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  1. Artikel: Persistent effects of repeated adolescent and adult heroin vapor inhalation in female Wistar rats.

    Gutierrez, Arnold / Taffe, Michael A

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Adolescent drug exposure has been associated with more severe mental health outcomes related to substance abuse and anxiety disorders. The aim of the present study was to contrast the long-term effects of repeated heroin vapor inhalation during ... ...

    Abstract Adolescent drug exposure has been associated with more severe mental health outcomes related to substance abuse and anxiety disorders. The aim of the present study was to contrast the long-term effects of repeated heroin vapor inhalation during adolescence with similar heroin exposure in adulthood. Groups of female Wistar rats underwent twice daily 30-minute sessions of heroin or propylene glycol (control) vapor inhalation from postnatal days (PND) 36-45 or PND 85-94, respectively. Nociception was assessed after vapor inhalation sessions and forty days later, for the Adolescent-Exposed and Adult-Exposed groups. Anxiety-like behavior was assessed with an elevated plus-maze (EPM) and spatial learning was assessed with a Barnes maze. Acute effects of naloxone (0.3 mg/kg, i.p.) and heroin (0.5 and 1.0 mg/kg, s.c.) on thermal nociception were determined on PND 140/189 and PND 149/198, respectively. Repeated heroin vapor inhalation produced anti-nociceptive tolerance across sessions in both adolescent and adult rats, with the adolescents exhibiting more complete tolerance. Heroin vapor inhalation produced anxiolytic effects, regardless of age of exposure. There were no effects of heroin on spatial learning. Naloxone produced acute hyperalgesia in all but the Adolescent-Exposed heroin group, and heroin anti-nociception was blunted in both heroin-exposed groups at the highest heroin dose. Repeated heroin vapor inhalation can produce lasting effects on nociception and anxiety-like behavior that persist for months after the exposure. Importantly, these findings suggest that adolescent exposure to heroin vapor produces specific effects on nociception that are not observed when exposure occurs in adulthood.
    Sprache Englisch
    Erscheinungsdatum 2024-05-10
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2024.05.06.592492
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Rats Chasing the Dragon: A new heroin inhalation method.

    Gutierrez, Arnold / Taffe, Michael A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Rationale: Despite extensive human use of the inhalation route for ingesting opioids, models in rodents have mostly been limited to parenteral injection and oral dosing. Methods using electronic drug delivery systems (EDDS; "e-cigarettes") have shown ... ...

    Abstract Rationale: Despite extensive human use of the inhalation route for ingesting opioids, models in rodents have mostly been limited to parenteral injection and oral dosing. Methods using electronic drug delivery systems (EDDS; "e-cigarettes") have shown efficacy in rodent models but these do not faithfully mimic the most popular human inhalation method of heating heroin to the point of vaporization.
    Objective: This study was designed to determine if direct volatilization of heroin hydrochloride delivers effective heroin doses to rodents.
    Methods: Middle aged rats were exposed to vapor created by direct heating of heroin HCl powder in a ceramic e-cigarette type atomizer. Efficacy was determined with a warm water tail withdrawal nociception assay, rectal temperature and self-administration.
    Results: Ten minutes of inhalation of vaporized heroin slowed response latency in a warm water tail withdrawal assay and increased rectal temperature in male rats, in a dose-dependent manner. Similar antinociceptive effects in female rats were attenuated by the opioid antagonist naloxone (1.0 mg/kg, s.c.). Female rats made operant responses for heroin vapor in 15-minute sessions, increased their response rate when the reinforcement ratio increased from FR1 to FR5, and further increased their responding when vapor delivery was omitted. Anti-nociceptive effects of self-administered volatilized heroin were of a similar magnitude as those produced by the 10-minute non-contingent exposure.
    Conclusions: This study shows that "chasing the dragon" methods of inhalation of heroin can be modeled successfully in the rat. Inhalation techniques may be particularly useful for longer term studies deep into middle age of rat species.
    Sprache Englisch
    Erscheinungsdatum 2023-08-14
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.08.09.552712
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Rats chasing the dragon: A new heroin inhalation method.

    Gutierrez, Arnold / Taffe, Michael A

    Journal of neuroscience methods

    2023  Band 402, Seite(n) 110013

    Abstract: Background: Despite extensive human use of inhalation for ingesting opioids, models in rodents have mostly been limited to parenteral injection and oral dosing. Methods using electronic drug delivery systems (EDDS; "e-cigarettes") have shown efficacy in ...

    Abstract Background: Despite extensive human use of inhalation for ingesting opioids, models in rodents have mostly been limited to parenteral injection and oral dosing. Methods using electronic drug delivery systems (EDDS; "e-cigarettes") have shown efficacy in rodent models but these do not faithfully mimic the most popular human inhalation method of heating heroin to the point of vaporization.
    New method: Middle aged rats were exposed to vapor created by direct heating of heroin HCl powder in a ceramic e-cigarette type atomizer. Efficacy was determined with a warm water tail withdrawal nociception assay, rectal temperature and self-administration.
    Results: Ten minutes of inhalation of vaporized heroin slowed response latency in a warm water tail withdrawal assay and increased rectal temperature in male rats, in a dose-dependent manner. Similar antinociceptive effects in female rats were attenuated by the opioid antagonist naloxone (1.0 mg/kg, s.c.). Female rats made operant responses for heroin vapor in 15-minute sessions, increased their response rate when the reinforcement ratio increased from FR1 to FR5, and further increased their responding when vapor delivery was omitted. Anti-nociceptive effects of self-administered volatilized heroin were of a similar magnitude as those produced by the 10-minute non-contingent exposure.
    Comparison with existing methods: Inhalation of directly volatilized heroin successfully produces heroin-typical effects, comparable to EDDS inhalation delivery.
    Conclusions: This study shows that "chasing the dragon" methods of inhalation of heroin can be modeled successfully in the rat. Inhalation techniques may be particularly useful for longer term studies deep into the middle age of rats.
    Mesh-Begriff(e) Humans ; Middle Aged ; Rats ; Male ; Female ; Animals ; Heroin/pharmacology ; Electronic Nicotine Delivery Systems ; Naloxone/pharmacology ; Narcotic Antagonists ; Camphor ; Menthol ; Water ; Self Administration
    Chemische Substanzen Heroin (70D95007SX) ; Naloxone (36B82AMQ7N) ; Narcotic Antagonists ; Camphor (76-22-2) ; Menthol (1490-04-6) ; Water (059QF0KO0R)
    Sprache Englisch
    Erscheinungsdatum 2023-11-19
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 282721-9
    ISSN 1872-678X ; 0165-0270
    ISSN (online) 1872-678X
    ISSN 0165-0270
    DOI 10.1016/j.jneumeth.2023.110013
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  4. Artikel ; Online: Adult consequences of repeated nicotine and Δ

    Gutierrez, Arnold / Creehan, Kevin M / Grant, Yanabel / Taffe, Michael A

    Psychopharmacology

    2024  Band 241, Heft 3, Seite(n) 585–599

    Abstract: Rationale: Use of electronic drug delivery systems (EDDS, "e-cigarettes") to ingest nicotine and Δ: Objectives: This study was conducted to examine the impact of repeated adolescent vapor inhalation of nicotine and THC in rats.: Methods: Female ... ...

    Abstract Rationale: Use of electronic drug delivery systems (EDDS, "e-cigarettes") to ingest nicotine and Δ
    Objectives: This study was conducted to examine the impact of repeated adolescent vapor inhalation of nicotine and THC in rats.
    Methods: Female Sprague-Dawley rats were exposed to 30-min sessions of vapor inhalation, twice daily, from post-natal day (PND) 31 to PND 40. Conditions included vapor from the propylene glycol (PG) vehicle, nicotine (60 mg/mL in the PG), THC (100 mg/mL in the PG), or the combination of nicotine (60 mg/mL) and THC (100 mg/mL). Rats were assessed on wheel activity, heroin anti-nociception and nicotine and heroin vapor volitional exposure during adulthood.
    Results: Nicotine-exposed rats exhibited few differences as adults, but were less sensitive to anti-nociceptive effects of heroin (1 mg/kg, s.c.). THC- and THC + nicotine-exposed rats were less spontaneously active, and obtained fewer nicotine vapor deliveries as adults. In contrast, THC-exposed rats obtained volitional heroin vapor at rates indistinguishable from the non-THC-exposed groups. Repeated THC exposure also caused tolerance to temperature-disrupting effects of THC (5 mg/kg, i.p.).
    Conclusions: These studies further confirm that the effects of repeated vapor exposure to THC in adolescence last into early to middle adulthood, including decreased volitional consumption of nicotine. Effects of repeated nicotine in adolescence were comparatively minor.
    Mesh-Begriff(e) Rats ; Animals ; Female ; Dronabinol/pharmacology ; Nicotine/pharmacology ; Rats, Sprague-Dawley ; Heroin ; Cannabis ; Electronic Nicotine Delivery Systems
    Chemische Substanzen Dronabinol (7J8897W37S) ; Nicotine (6M3C89ZY6R) ; Heroin (70D95007SX)
    Sprache Englisch
    Erscheinungsdatum 2024-01-29
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 130601-7
    ISSN 1432-2072 ; 0033-3158
    ISSN (online) 1432-2072
    ISSN 0033-3158
    DOI 10.1007/s00213-024-06545-5
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  5. Artikel: Adult consequences of repeated nicotine and Δ

    Gutierrez, Arnold / Creehan, Kevin M / Grant, Yanabel / Taffe, Michael A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The use of Electronic Drug Delivery Systems (EDDS, "e-cigarettes") to ingest nicotine and ... ...

    Abstract The use of Electronic Drug Delivery Systems (EDDS, "e-cigarettes") to ingest nicotine and Δ
    Sprache Englisch
    Erscheinungsdatum 2023-09-12
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.09.08.556932
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: Oxycodone Self-Administration in Female Rats is Enhanced by ∆

    Nguyen, Jacques D / Grant, Yanabel / Yang, Celine / Gutierrez, Arnold / Taffe, Michael A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Epidemiological evidence suggests that the legalization of cannabis may reduce opioid-related harms. Preclinical evidence of neuropharmacological interactions of endogenous cannabinoid and opioid systems prompts further investigation of cannabinoids as ... ...

    Abstract Epidemiological evidence suggests that the legalization of cannabis may reduce opioid-related harms. Preclinical evidence of neuropharmacological interactions of endogenous cannabinoid and opioid systems prompts further investigation of cannabinoids as potential therapeutics for the non-medical use of opioids. In these studies female rats, previously trained to self-administer oxycodone (0.15 mg/kg/infusion) intravenously in 6 h sessions, were allowed to self-administer oxycodone after exposure to cannabidiol (CBD) and Δ
    Sprache Englisch
    Erscheinungsdatum 2023-10-31
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.10.26.564282
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: The long-term effects of repeated heroin vapor inhalation during adolescence on measures of nociception and anxiety-like behavior in adult Wistar rats.

    Gutierrez, Arnold / Harvey, Eric L / Creehan, Kevin M / Taffe, Michael A

    Psychopharmacology

    2022  Band 239, Heft 12, Seite(n) 3939–3952

    Abstract: Rationale: Adolescents represent a vulnerable group due to increased experimentation with illicit substances that is often associated with the adolescent period, and because adolescent drug use can result in long-term effects that differ from those ... ...

    Abstract Rationale: Adolescents represent a vulnerable group due to increased experimentation with illicit substances that is often associated with the adolescent period, and because adolescent drug use can result in long-term effects that differ from those caused by drug use initiated during adulthood.
    Objectives: The purpose of the present study was to determine the effects of repeated heroin vapor inhalation during adolescence on measures of nociception, and anxiety-like behavior during adulthood in female and male Wistar rats.
    Methods: Rats were exposed twice daily to 30 min of heroin vapor from post-natal day (PND) 36 to PND 45. At 12 weeks of age, baseline thermal nociception was assessed across a range of temperatures with a warm-water tail-withdrawal assay. Anxiety-like behavior was assessed in an elevated plus-maze (EPM) and activity was measured in an open-field arena. Starting at 23 weeks of age, baseline thermal nociception was re-assessed, nociception was determined after acute heroin or naloxone injection, and anxiety-like behavior was redetermined in the EPM.
    Results: Adolescent heroin inhalation altered baseline thermal nociception in female rats at 12 weeks of age and in both female and male rats at ~ 23 weeks. Heroin-treated animals exhibited anxiety-like behavior when tested in the elevated plus-maze, showed blunted heroin-induced analgesia, but exhibited no effect on naloxone-induced hyperalgesia.
    Conclusions: The present study demonstrates that heroin vapor inhalation during adolescence produces behavioral and physiological consequences in rats that persist well into adulthood.
    Mesh-Begriff(e) Rats ; Animals ; Male ; Female ; Rats, Wistar ; Heroin/pharmacology ; Nociception ; Anxiety ; Naloxone/pharmacology
    Chemische Substanzen Heroin (70D95007SX) ; Naloxone (36B82AMQ7N)
    Sprache Englisch
    Erscheinungsdatum 2022-10-26
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 130601-7
    ISSN 1432-2072 ; 0033-3158
    ISSN (online) 1432-2072
    ISSN 0033-3158
    DOI 10.1007/s00213-022-06267-6
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  8. Artikel ; Online: Adult Consequences of Repeated Nicotine Vapor Inhalation in Adolescent Rats.

    Gutierrez, Arnold / Nguyen, Jacques D / Creehan, Kevin M / Grant, Yanabel / Taffe, Michael A

    Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

    2023  Band 26, Heft 6, Seite(n) 715–723

    Abstract: Introduction: There has been a resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Almost five times as many US high-school seniors inhale nicotine vapor daily compared ... ...

    Abstract Introduction: There has been a resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Almost five times as many US high-school seniors inhale nicotine vapor daily compared with those who smoke tobacco. This study was conducted to determine the impact of repeated adolescent vapor inhalation of nicotine on behavior in adulthood.
    Methods: Male and female Sprague-Dawley rats were exposed to 30-minute sessions of ENDS vapor inhalation, twice daily, from post-natal day (PND) 31-40. Conditions included vapor from the propylene glycol (PG) vehicle or nicotine (30 mg/mL in the PG). Animals were assessed for effects of nicotine on open field (PND 74-105) and wheel activity (PND 126-180) and for volitional exposure to nicotine vapor (PND 285-395). Plasma nicotine and cotinine were assessed in separate groups of male and female Wistar and Sprague-Dawley rats after a single nicotine inhalation session.
    Results: Group mean plasma nicotine ranged from 39 to 59 ng/mL post-session with minimal strain differences detected. Adolescent nicotine exposure enhanced sensitivity to the locomotor stimulating effects of nicotine (0.1-0.8 mg/kg, s.c.) in an open field in female rats, but didn't change the effects of nicotine on wheel activity. Female rats exposed to nicotine (30 mg/mL) vapor as adolescents responded more vigorously than PG-exposed females to nicotine vapor in a fixed ratio 5 challenge.
    Conclusions: Repeated adolescent nicotine vapor inhalation leads to enhanced liability for volitional exposure to nicotine vapor in adulthood in female rats, but minimal change in spontaneous locomotor behavior.
    Implications: These results show that adolescent vaping of nicotine can lead to lasting sensitization to the effects of nicotine in adulthood, including volitional responding for nicotine vapor. Demonstration of this in a controlled animal model establishes causality in a manner not possible from longitudinal evidence in human populations. These findings further highlight the importance of decreasing adolescent nicotine exposure to e-cigarettes to reduce consumption in adulthood.
    Mesh-Begriff(e) Animals ; Female ; Male ; Nicotine/administration & dosage ; Rats, Sprague-Dawley ; Rats ; Electronic Nicotine Delivery Systems ; Administration, Inhalation ; Rats, Wistar ; Behavior, Animal/drug effects ; Cotinine/blood ; Vaping
    Sprache Englisch
    Erscheinungsdatum 2023-11-09
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 1452315-2
    ISSN 1469-994X ; 1462-2203
    ISSN (online) 1469-994X
    ISSN 1462-2203
    DOI 10.1093/ntr/ntad211
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: A vapor exposure method for delivering heroin alters nociception, body temperature and spontaneous activity in female and male rats.

    Gutierrez, Arnold / Creehan, Kevin M / Taffe, Michael A

    Journal of neuroscience methods

    2020  Band 348, Seite(n) 108993

    Abstract: Background: The ongoing crisis related to non-medical use of opioids makes it of continued importance to understand the risk factors for opioid addiction, the behavioral and neurobiological consequences of opioid exposure and to seek potential avenues ... ...

    Abstract Background: The ongoing crisis related to non-medical use of opioids makes it of continued importance to understand the risk factors for opioid addiction, the behavioral and neurobiological consequences of opioid exposure and to seek potential avenues for therapy. Pre-clinical rodent models have been critical to advancing understanding of opioid consequences for decades, but have been mostly limited to drug delivery by injection or by oral dosing. Inhalation, a significant route for many human users, has not been as well-established.
    Method: We adapted an e-cigarette based exposure system, previously shown efficacious for delivery of other drugs to rats, to deliver heroin vapor. Effectsin vivo were assessed in male and female Sprague-Dawley rats using a warm-water assay for anti-nociception and an implanted radiotelemetry system for evaluating changes in body temperature and spontaneous activity rate.
    Results: Inhalation of vapor created by heroin 100 mg/mL in the propylene glycol (PG) vehicle significantly slowed tail-withdrawal from a 52 °C water bath, bi-phasically altered activity, and increased temperature in male and female rats. Inhalation of heroin 50 mg/mL for 15 min produced significant effects, as the lower bound on efficacy, whereas inhalation of heroin 100 mg/mL for 30 min produced robust effects across all endpoints and groups.
    Conclusions: This work shows that e-cigarette devices deliver psychoactive doses of heroin to rats, using concentrations of ∼50-100 mg/mL and inhalation durations of 15-30 min. This technique may be useful to assess the health consequences of inhaled heroin and other opioid drugs.
    Mesh-Begriff(e) Analgesics, Opioid/pharmacology ; Animals ; Body Temperature ; Electronic Nicotine Delivery Systems ; Female ; Heroin/toxicity ; Male ; Nociception ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Temperature
    Chemische Substanzen Analgesics, Opioid ; Heroin (70D95007SX)
    Sprache Englisch
    Erscheinungsdatum 2020-10-30
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 282721-9
    ISSN 1872-678X ; 0165-0270
    ISSN (online) 1872-678X
    ISSN 0165-0270
    DOI 10.1016/j.jneumeth.2020.108993
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  10. Artikel ; Online: Behavioral effects of ethanol in the Red Swamp Crayfish (Procambarus clarkii).

    Gutierrez, Arnold / Creehan, Kevin M / de Guglielmo, Giordano / Roberts, Amanda J / Taffe, Michael A

    Journal of the experimental analysis of behavior

    2022  Band 117, Heft 3, Seite(n) 472–492

    Abstract: Alcohol abuse remains one of the primary preventable sources of mortality in the United States. Model species can be used to evaluate behavioral and other biological changes associated with alcohol and to identify novel treatments. This report describes ... ...

    Abstract Alcohol abuse remains one of the primary preventable sources of mortality in the United States. Model species can be used to evaluate behavioral and other biological changes associated with alcohol and to identify novel treatments. This report describes methods for evaluating the behavioral effects of ethanol (EtOH) in crayfish. Crayfish (Procambarus clarkii) were immersed in ethanol concentrations ranging from 0.1 to 1.0 molar, for 10-30 min. Studies evaluated hemolymph alcohol concentration, locomotion in an open field and anxiety-like behavior using a Light/Dark transfer approach. EtOH immersion produced dose-dependent increases in hemolymph EtOH (up to 249 mg/dL) and reductions in open field locomotion that depended on EtOH concentration or exposure duration. Untreated crayfish exhibit avoidance of the open parts of the locomotor arena and a preference for a covered portion. Acute EtOH immersion decreased time spent in the covered portion of the Light/Dark arena, consistent with a decrease in anxiety-like behavior. Daily EtOH immersion for 5 days did not alter locomotor responses, however, activity was increased 3 days after the repeated EtOH regimen. Overall, this study shows that this inexpensive, easily maintained species can be used for behavioral pharmacological experiments designed to assess the acute and repeated effects of EtOH.
    Mesh-Begriff(e) Animals ; Anxiety ; Astacoidea/physiology ; Ethanol/pharmacology ; Locomotion
    Chemische Substanzen Ethanol (3K9958V90M)
    Sprache Englisch
    Erscheinungsdatum 2022-03-09
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 219405-3
    ISSN 1938-3711 ; 0022-5002
    ISSN (online) 1938-3711
    ISSN 0022-5002
    DOI 10.1002/jeab.746
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