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Article ; Online: Heterogeneous Habenular Neuronal Ensembles during Selection of Defensive Behaviors.

Lecca, Salvatore / Namboodiri, Vijay M K / Restivo, Leonardo / Gervasi, Nicolas / Pillolla, Giuliano / Stuber, Garret D / Mameli, Manuel

Cell reports

2020 Volume 31, Issue 10, Page(s) 107752

Abstract: Optimal selection of threat-driven defensive behaviors is paramount to an animal's survival. The lateral habenula (LHb) is a key neuronal hub coordinating behavioral responses to aversive stimuli. Yet, how individual LHb neurons represent defensive ... ...

Abstract	Optimal selection of threat-driven defensive behaviors is paramount to an animal's survival. The lateral habenula (LHb) is a key neuronal hub coordinating behavioral responses to aversive stimuli. Yet, how individual LHb neurons represent defensive behaviors in response to threats remains unknown. Here, we show that in mice, a visual threat promotes distinct defensive behaviors, namely runaway (escape) and action-locking (immobile-like). Fiber photometry of bulk LHb neuronal activity in behaving animals reveals an increase and a decrease in calcium signal time-locked with runaway and action-locking, respectively. Imaging single-cell calcium dynamics across distinct threat-driven behaviors identify independently active LHb neuronal clusters. These clusters participate during specific time epochs of defensive behaviors. Decoding analysis of this neuronal activity reveals that some LHb clusters either predict the upcoming selection of the defensive action or represent the selected action. Thus, heterogeneous neuronal clusters in LHb predict or reflect the selection of distinct threat-driven defensive behaviors.
MeSH term(s)	Animals ; Behavior, Animal/physiology ; Habenula/physiology ; Mice ; Neurons/metabolism
Language	English
Publishing date	2020-06-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.107752
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Article ; Online: Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat: involvement of the endocannabinoid system.

Perra, Simona / Pillolla, Giuliano / Luchicchi, Antonio / Pistis, Marco

Alcoholism, clinical and experimental research

2008 Volume 32, Issue 3, Page(s) 443–449

Abstract: Background: A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological ... ...

Abstract	Background: A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological mechanisms of drugs of abuse, including alcohol and cannabinoids. It is recently emerging that the endocannabinoid system is involved in many pharmacological and behavioral effects of alcohol. The BLA possesses a very high density of CB1 cannabinoid receptors, and endocannabinoids modulate forms of synaptic plasticity in this region. The aims of our study were first to investigate in vivo the sensitivity of BLA pyramidal neurons to alcohol and second to determine the role of the endocannabinoid system in the acute effects of alcohol. Methods: We utilized extracellular single cell recordings in urethane anesthetized rats from BLA principal neurons, antidromically identified from their projection site in the nucleus accumbens. Results: Alcohol (0.25 to 2.0 g/kg i.v.) induced a marked decrease in the spontaneous firing rate of BLA projecting neurons (51.1 +/- 16% of baseline at 0.5 g/kg alcohol, p < 0.0001). The involvement of the endogenous cannabinoid system was investigated by administering the CB1 receptor antagonist SR141716A (rimonabant, SR) (1.0 mg/kg i.v.) before alcohol. SR per se did not significantly affect firing rate of BLA neurons, but it prevented the inhibition produced by alcohol (98 +/- 18% of baseline firing at 0.5 g/kg alcohol, p < 0.01). Then, we studied the actions of alcohol following a chronic treatment with the CB1 agonist WIN55212-2 (WIN). Animals were administered WIN for 6.5 days (2.0 mg/kg, i.p. twice daily) and alcohol dose-response curves were carried out on firing rate of BLA neurons 24 hours following the last injection of the cannabinoid agonist. In WIN-treated animals the inhibitory effect of alcohol was significantly reduced as compared with controls (95 +/- 16% of baseline firing at 0.5 g/kg, p < 0.05). Conclusions: Our results provide evidence of the involvement of the endocannabinoid system in the effects of alcohol on BLA projection neurons. They also further point to the endocannabinoid system as a possible molecular target in the treatment of alcoholism.
MeSH term(s)	Action Potentials/drug effects ; Action Potentials/physiology ; Alcohol Drinking/physiopathology ; Amygdala/drug effects ; Amygdala/physiology ; Animals ; Cannabinoid Receptor Modulators/antagonists & inhibitors ; Cannabinoid Receptor Modulators/physiology ; Dose-Response Relationship, Drug ; Endocannabinoids ; Ethanol/pharmacology ; Male ; Neural Inhibition/drug effects ; Neural Inhibition/physiology ; Neural Pathways/drug effects ; Neural Pathways/physiology ; Neurons/drug effects ; Neurons/physiology ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/physiology ; Piperidines/pharmacology ; Pyrazoles/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/antagonists & inhibitors ; Receptor, Cannabinoid, CB1/physiology
Chemical Substances	Cannabinoid Receptor Modulators ; Endocannabinoids ; Piperidines ; Pyrazoles ; Receptor, Cannabinoid, CB1 ; Ethanol (3K9958V90M) ; rimonabant (RML78EN3XE)
Language	English
Publishing date	2008-03
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/j.1530-0277.2007.00588.x
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Article ; Online: Inhibition of 17α-hydroxylase/C17,20 lyase reduces gating deficits consequent to dopaminergic activation.

Frau, Roberto / Bini, Valentina / Pes, Romina / Pillolla, Giuliano / Saba, Pierluigi / Devoto, Paola / Bortolato, Marco

Psychoneuroendocrinology

2013 Volume 39, Page(s) 204–213

Abstract: Cogent evidence points to the involvement of neurosteroids in the regulation of dopamine (DA) neurotransmission and signaling, yet the neurobiological bases of this link remain poorly understood. We previously showed that inhibition of 5α-reductase (5αR), ...

Abstract	Cogent evidence points to the involvement of neurosteroids in the regulation of dopamine (DA) neurotransmission and signaling, yet the neurobiological bases of this link remain poorly understood. We previously showed that inhibition of 5α-reductase (5αR), a key neurosteroidogenic enzyme, attenuates the sensorimotor gating deficits induced by DA receptor activation, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. To extend these findings, the present study was aimed at the assessment of the role of other key neurosteroidogenic enzymes in PPI, such as 17α-hydroxylase/C17,20 lyase (CYP17A1), 3α- and 3β-hydroxysteroid dehydrogenase (HSD), in Sprague-Dawley rats. The PPI deficits induced by the DAergic non-selective agonist apomorphine (APO, 0.25mg/kg, SC) were dose-dependently attenuated by the selective CYP17A1 inhibitor abiraterone (ABI, 10-50mg/kg, IP) in a fashion akin to that of the 5αR inhibitor finasteride (FIN, 100mg/kg, IP). These systemic effects were reproduced by intracerebroventricular injection of ABI (1 μg/1 μl), suggesting the involvement of brain CYP17A1 in PPI regulation. Conversely, the PPI disruption induced by APO was not significantly affected by the 3α- and 3β-HSD inhibitors indomethacin and trilostane. Given that CYP17A1 catalyzes androgen synthesis, we also tested the impact on PPI of the androgen receptor (AR) antagonist flutamide (10mg/kg, IP). However, this agent failed to reverse APO-induced PPI deficits; furthermore, AR endogenous ligands testosterone and dihydrotestosterone failed to disrupt PPI. Collectively, these data highlight CYP17A1 as a novel target for antipsychotic-like action, and suggest that the DAergic regulation of PPI is modulated by androgenic neurosteroids, through AR-unrelated mechanisms.
MeSH term(s)	5-alpha Reductase Inhibitors/pharmacology ; Androstenes ; Androstenols/pharmacology ; Animals ; Apomorphine/pharmacology ; Dopamine Agonists/pharmacology ; Finasteride/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Reflex, Startle/drug effects ; Sensory Gating/drug effects ; Steroid 17-alpha-Hydroxylase/antagonists & inhibitors
Chemical Substances	5-alpha Reductase Inhibitors ; Androstenes ; Androstenols ; Dopamine Agonists ; Finasteride (57GNO57U7G) ; Steroid 17-alpha-Hydroxylase (EC 1.14.14.19) ; abiraterone (G819A456D0) ; Apomorphine (N21FAR7B4S)
Language	English
Publishing date	2013-09-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2013.09.014
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Article ; Online: The neurosteroidogenic enzyme 5α-reductase modulates the role of D1 dopamine receptors in rat sensorimotor gating.

Frau, Roberto / Mosher, Laura J / Bini, Valentina / Pillolla, Giuliano / Pes, Romina / Saba, Pierluigi / Fanni, Silvia / Devoto, Paola / Bortolato, Marco

Psychoneuroendocrinology

2015 Volume 63, Page(s) 59–67

Abstract: Neurosteroids exert diverse modulatory actions on dopamine neurotransmission and signaling. We previously documented that the enzyme 5α-reductase, which catalyzes the main rate-limiting step in neurosteroid synthesis, is required for the behavioral ... ...

Abstract	Neurosteroids exert diverse modulatory actions on dopamine neurotransmission and signaling. We previously documented that the enzyme 5α-reductase, which catalyzes the main rate-limiting step in neurosteroid synthesis, is required for the behavioral responses of Sprague-Dawley rats to non-selective dopaminergic agonists, such as the D1-D2 receptor agonist apomorphine. Specifically, systemic and intra-accumbal administrations of the 5α-reductase inhibitor finasteride countered apomorphine-induced deficits of sensorimotor gating, as measured by the prepulse inhibition (PPI) of the startle reflex; the classes of dopamine receptors involved in these effects, however, remain unknown. Prior rodent studies have revealed that the contributions of dopamine receptors to PPI regulation vary depending on the genetic background; thus, we analyzed the effect of finasteride on the PPI deficits induced by selective dopamine receptor agonists in Long-Evans (a strain exhibiting PPI deficits in response to both D1 and D2 receptor agonists) and Sprague-Dawley rats (which display PPI reductions following treatment with D2, and D3, but not D1 receptor agonists). In Long-Evans rats, finasteride opposed the PPI deficits induced by activation of D1, but not D2 receptors; conversely, in Sprague-Dawley rats, finasteride prevented the reductions in %PPI and accumbal dopamine extracellular levels caused by selective stimulation of D3, but not D2 receptors; however, the effects on %PPI were not confirmed by analyses on absolute PPI values. Our findings suggest that 5α-reductase modulates the effects of D1, but not D2 receptor agonists on sensorimotor gating. These data may help elucidate the role of neurosteroids in neuropsychiatric disorders featuring PPI deficits, including schizophrenia and Tourette syndrome.
MeSH term(s)	3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism ; 5-alpha Reductase Inhibitors/pharmacology ; Animals ; Dopamine Agonists/pharmacology ; Finasteride/pharmacology ; Male ; Microdialysis ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Prepulse Inhibition/drug effects ; Prepulse Inhibition/physiology ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; Receptors, Dopamine D1/drug effects ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D2/drug effects ; Receptors, Dopamine D2/metabolism ; Receptors, Dopamine D3/drug effects ; Receptors, Dopamine D3/metabolism ; Reflex, Startle/drug effects ; Reflex, Startle/physiology ; Sensory Gating/drug effects ; Sensory Gating/physiology
Chemical Substances	5-alpha Reductase Inhibitors ; Dopamine Agonists ; Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Receptors, Dopamine D3 ; Finasteride (57GNO57U7G) ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase (EC 1.3.99.5)
Language	English
Publishing date	2015-09-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2015.09.014
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Article ; Online: Inhibition of 5α-reductase attenuates behavioral effects of D1-, but not D2-like receptor agonists in C57BL/6 mice.

Frau, Roberto / Pillolla, Giuliano / Bini, Valentina / Tambaro, Simone / Devoto, Paola / Bortolato, Marco

Psychoneuroendocrinology

2012 Volume 38, Issue 4, Page(s) 542–551

Abstract: Converging lines of evidence point to the involvement of neurosteroids in the regulation of dopamine (DA) neurotransmission and signaling, yet the neurobiological bases of this link remain poorly understood. We previously showed that inhibition of ... ...

Abstract	Converging lines of evidence point to the involvement of neurosteroids in the regulation of dopamine (DA) neurotransmission and signaling, yet the neurobiological bases of this link remain poorly understood. We previously showed that inhibition of steroid 5α-reductase (5αR), the key rate-limiting enzyme in neurosteroidogenesis, attenuates the behavioral effects of non-selective DA receptor agonists in rats, including stereotyped responses and sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. Since previous findings suggested that the role of DA D(1)- and D(2)-like receptor families in behavioral regulation may exhibit broad interspecies and interstrain variations, we assessed the impact of 5αR blockade on the behavioral effects of DAergic agonists in C57BL/6 mice. The prototypical 5αR inhibitor finasteride (FIN; 25-50 mg/kg, intraperitoneally, IP) dose-dependently countered the PPI deficits and the enhancement of rearing responses induced by the full D(1)-like receptor agonist SKF-82958 (0.3 mg/kg, IP); however, FIN did not significantly affect the hyperlocomotive and startle-attenuating effects of SKF-82958. Whereas the D(2)-like receptor agonist quinpirole (QUIN; 0.5 mg/kg, IP) did not induce significant changes in PPI, the combination of this agent and FIN surprisingly produced marked gating and startle deficits. In contrast with previous data on rats, FIN did not affect the reductions of startle reflex and PPI produced by the non-selective DAergic agonist apomorphine (APO; 0.5 mg/kg, IP). These findings collectively indicate that, in C57BL/6 mice, 5αR differentially modulates the effects of D(1)- and D(2)-like receptor agonists in behavioral regulation.
MeSH term(s)	5-alpha Reductase Inhibitors/pharmacology ; Animals ; Apomorphine/pharmacology ; Benzazepines/antagonists & inhibitors ; Benzazepines/pharmacology ; Catalepsy/prevention & control ; Dopamine Agonists/pharmacology ; Dopamine Antagonists/pharmacology ; Dose-Response Relationship, Drug ; Drug Interactions ; Finasteride/pharmacology ; Haloperidol/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Quinpirole/pharmacology ; Sensory Gating/drug effects ; Stereotyped Behavior/drug effects
Chemical Substances	5-alpha Reductase Inhibitors ; Benzazepines ; Dopamine Agonists ; Dopamine Antagonists ; Quinpirole (20OP60125T) ; Finasteride (57GNO57U7G) ; SK&F 82958 (80751-65-1) ; Haloperidol (J6292F8L3D) ; Apomorphine (N21FAR7B4S)
Language	English
Publishing date	2012-08-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2012.07.014
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Article ; Online: Positive allosteric modulation of GABAB receptors ameliorates sensorimotor gating in rodent models.

Frau, Roberto / Bini, Valentina / Pillolla, Giuliano / Malherbe, Pari / Pardu, Alessandra / Thomas, Andrew W / Devoto, Paola / Bortolato, Marco

CNS neuroscience & therapeutics

2014 Volume 20, Issue 7, Page(s) 679–684

Abstract: Background: Converging evidence points to the involvement of γ-amino-butyric acid B receptors (GABABRs) in the regulation of information processing. We previously showed that GABABR agonists exhibit antipsychotic-like properties in rodent models of ... ...

Abstract	Background: Converging evidence points to the involvement of γ-amino-butyric acid B receptors (GABABRs) in the regulation of information processing. We previously showed that GABABR agonists exhibit antipsychotic-like properties in rodent models of sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. The therapeutic potential of these agents, however, is limited by their neuromuscular side effects; thus, in this study, we analyzed whether rac-BHFF, a potent GABABR-positive allosteric modulator (PAM), could counter spontaneous and pharmacologically induced PPI deficits across various rodent models. Methods: We tested the antipsychotic effects of rac-BHFF on the PPI deficits caused by the N-methyl-D-aspartate glutamate receptor antagonist dizocilpine, in Sprague-Dawley rats and C57BL/6 mice. Furthermore, we verified whether rac-BHFF ameliorated the spontaneous PPI impairments in DBA/2J mice. Results: rac-BHFF dose-dependently countered the PPI deficits across all three models, in a fashion akin to the GABABR agonist baclofen and the atypical antipsychotic clozapine; in contrast with these compounds, however, rac-BHFF did not affect startle magnitude. Conclusions: The present data further support the implication of GABABRs in the modulation of sensorimotor gating and point to their PAMs as a novel promising tool for antipsychotic treatment, with fewer side effects than GABABR agonists.
MeSH term(s)	Allosteric Regulation/drug effects ; Allosteric Regulation/physiology ; Animals ; Benzofurans/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Models, Animal ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-B/physiology ; Sensory Gating/drug effects ; Sensory Gating/physiology
Chemical Substances	(R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one ; Benzofurans ; Receptors, GABA-B
Language	English
Publishing date	2014-04-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2423461-8
ISSN	1755-5949 ; 1755-5930
ISSN (online)	1755-5949
ISSN	1755-5930
DOI	10.1111/cns.12261
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Article ; Online: Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant nocturnal frontal lobe epilepsy.

Puligheddu, Monica / Melis, Miriam / Pillolla, Giuliano / Milioli, Giulia / Parrino, Liborio / Terzano, Giovanni Mario / Aroni, Sonia / Sagheddu, Claudia / Marrosu, Francesco / Pistis, Marco / Muntoni, Anna Lisa

Epilepsia

2017 Volume 58, Issue 10, Page(s) 1762–1770

Abstract: Objective: Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in ... ...

Abstract	Objective: Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in about 55% of patients, whereas the rest remains refractory. One of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic acetylcholine receptors (nAChRs) containing the mutated α4 or β2 subunits. Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome proliferator-activated receptor alpha (PPARα) that is a ligand-activated transcription factor, which negatively modulates the function of β2-containing nAChR. To test clinical efficacy of adjunctive therapy with fenofibrate in pharmacoresistant ADNFLE\NFLE patients, we first demonstrated the effectiveness of fenofibrate in a mutated mouse model displaying both disease genotype and phenotype. Methods: We first tested the efficacy of fenofibrate in transgenic mice carrying the mutation in the α4-nAChR subunit (Chrna4S252F) homologous to that found in humans. Subsequently, an add-on protocol was implemented in a clinical setting and fenofibrate was administered to pharmacoresistant NFLE patients. Results: Here, we show that a chronic fenofibrate diet markedly reduced the frequency of large inhibitory postsynaptic currents (IPSCs) recorded from cortical pyramidal neurons in Chrna4S252F mice, and prevented nicotine-induced increase of IPSC frequency. Moreover, fenofibrate abolished differences between genotypes in the frequency of sleep-related movements observed under basal conditions. Patients affected by NFLE, nonresponders to traditional therapy, by means of adjunctive therapy with fenofibrate displayed a reduction of seizure frequency. Furthermore, digital video-polysomnographic recordings acquired in NFLE subjects after 6 months of adjunctive fenofibrate substantiated the significant effects on control of motor-behavioral seizures. Significance: Our preclinical and clinical studies suggest PPARα as a novel disease-modifying target for antiepileptic drugs due to its ability to regulate dysfunctional nAChRs.
MeSH term(s)	Adult ; Animals ; Anticonvulsants/pharmacology ; Benzodiazepines/therapeutic use ; Carbamazepine/analogs & derivatives ; Carbamazepine/therapeutic use ; Disease Models, Animal ; Drug Resistant Epilepsy/drug therapy ; Drug Resistant Epilepsy/genetics ; Drug Therapy, Combination ; Electroencephalography ; Epilepsy, Frontal Lobe/drug therapy ; Epilepsy, Frontal Lobe/genetics ; Female ; Fenofibrate/pharmacology ; Fenofibrate/therapeutic use ; Humans ; Male ; Mice ; Mice, Transgenic ; Middle Aged ; Mutation ; PPAR alpha/agonists ; Piracetam/analogs & derivatives ; Piracetam/therapeutic use ; Polysomnography ; Receptors, Nicotinic/genetics ; Triazines/therapeutic use ; Valproic Acid/therapeutic use ; Young Adult
Chemical Substances	Anticonvulsants ; PPAR alpha ; Receptors, Nicotinic ; Triazines ; nicotinic acetylcholine receptor alpha4 subunit ; Benzodiazepines (12794-10-4) ; etiracetam (230447L0GL) ; clobazam (2MRO291B4U) ; Carbamazepine (33CM23913M) ; Valproic Acid (614OI1Z5WI) ; Fenofibrate (U202363UOS) ; lamotrigine (U3H27498KS) ; oxcarbazepine (VZI5B1W380) ; Piracetam (ZH516LNZ10)
Language	English
Publishing date	2017-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.13863
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Zs.A 517: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Electrophysiological properties of dopamine neurons in the ventral tegmental area of Sardinian alcohol-preferring rats.

Melis, Miriam / Pillolla, Giuliano / Perra, Simona / Colombo, Giancarlo / Muntoni, Anna Lisa / Pistis, Marco

Psychopharmacology

2008 Volume 201, Issue 4, Page(s) 471–481

Abstract: Rationale: Sardinian alcohol-preferring (sP) or -nonpreferring (sNP) rats are one of the few pairs of lines of rats selectively bred for their voluntary alcohol preference or aversion, respectively. Ventral tegmental area (VTA) dopamine (DA) neurons ... ...

Abstract	Rationale: Sardinian alcohol-preferring (sP) or -nonpreferring (sNP) rats are one of the few pairs of lines of rats selectively bred for their voluntary alcohol preference or aversion, respectively. Ventral tegmental area (VTA) dopamine (DA) neurons have long been implicated in many drug-related behaviors, including alcohol self-administration. However, the electrophysiological properties of these cells in sP and sNP rats remain unknown. Objectives: This study was designed to examine the properties of posterior VTA DA neurons and to unveil functional differences between sP and sNP rats. Materials and methods: The electrophysiological properties of DA cells were examined performing either single-cell extracellular recordings in anesthetized rats or whole-cell patch-clamp recordings in slices. Results: Extracellular single-unit recordings revealed an increased spontaneous activity in sP rats. However, a corresponding difference was not found in vitro. Moreover, DA cells of sP and sNP rats showed similar intrinsic properties, suggesting changes at synaptic level. Therefore, inhibitory- and excitatory-mediated currents were studied. A decreased probability of GABA release was found in sP rats. Additionally, sP rats showed a reduced depolarization-induced suppression of inhibition, which is an endocannabinoid-mediated form of short-term plasticity. Additionally, the effect of cannabinoid-type 1 (CB1) receptor agonist WIN55,212-2 on GABAA IPSCs was smaller in sP rats, suggesting either a reduced number or functionality of CB1 receptors in the VTA. Conclusions: Our findings suggest that both decreased GABA release and endocannabinoid transmission in the VTA play a role in the increased impulse activity of DA cells and, ultimately, in alcohol preference displayed by sP rats.
MeSH term(s)	Alcohol Drinking ; Animals ; Dopamine/metabolism ; Electrophysiology ; Inhibitory Postsynaptic Potentials/drug effects ; Male ; Neurons/metabolism ; Patch-Clamp Techniques ; Rats ; Receptor, Cannabinoid, CB1/drug effects ; Receptor, Cannabinoid, CB1/metabolism ; Receptors, GABA-A/drug effects ; Receptors, GABA-A/metabolism ; Ventral Tegmental Area/metabolism
Chemical Substances	Receptor, Cannabinoid, CB1 ; Receptors, GABA-A ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2008-09-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	130601-7
ISSN	1432-2072 ; 0033-3158
ISSN (online)	1432-2072
ISSN	0033-3158
DOI	10.1007/s00213-008-1309-2
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Article ; Online: Inhibition of 5α-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation.

Devoto, Paola / Frau, Roberto / Bini, Valentina / Pillolla, Giuliano / Saba, Pierluigi / Flore, Giovanna / Corona, Marta / Marrosu, Francesco / Bortolato, Marco

Psychoneuroendocrinology

2011 Volume 37, Issue 10, Page(s) 1630–1645

Abstract: Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic- ... ...

Abstract	Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5αR inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (ΔPPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25mg/kg, SC) and d-amphetamine (AMPH, 2.5mg/kg, SC), although the latter effect was not corroborated by ΔPPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10μg/1μl) and in the nucleus accumbens (NAc) shell and core (0.5μg/0.5μl/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5αR in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region.
MeSH term(s)	5-alpha Reductase Inhibitors/pharmacology ; Animals ; Apomorphine/pharmacology ; Cholestenone 5 alpha-Reductase/metabolism ; Dextroamphetamine/pharmacology ; Dopamine Agents/pharmacology ; Finasteride/pharmacology ; Male ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/enzymology ; Orchiectomy ; Rats ; Rats, Sprague-Dawley ; Reflex, Startle/drug effects ; Sensory Gating/drug effects
Chemical Substances	5-alpha Reductase Inhibitors ; Dopamine Agents ; Finasteride (57GNO57U7G) ; Cholestenone 5 alpha-Reductase (EC 1.3.1.22) ; Apomorphine (N21FAR7B4S) ; Dextroamphetamine (TZ47U051FI)
Language	English
Publishing date	2011-10-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2011.09.018
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion

Quartu Marina / Serra Maria P / Boi Marianna / Pillolla Giuliano / Melis Tiziana / Poddighe Laura / Del Fiacco Marina / Falconieri Danilo / Carta Gianfranca / Murru Elisabetta / Cordeddu Lina / Piras Antonio / Collu Maria / Banni Sebastiano

Lipids in Health and Disease, Vol 11, Iss 1, p

2012 Volume 8

Abstract: Abstract Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of ... ...

Abstract	Abstract Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Methods Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. Results BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). Conclusions Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.
Keywords	Bilateral common carotid artery occlusion ; reperfusion ; DHA; COX-2 ; PEA ; OEA ; Pistacia lentiscus L. ; cerebral cortex ; Wistar rat ; Physiology ; QP1-981 ; Science ; Q ; DOAJ:Physiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Subject code	610
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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