Adolescent Δ(9)-Tetrahydrocannabinol Exposure Alters WIN55,212-2 Self-Administration in Adult Rats

Maria Scherma, Christian Dessì, Anna Lisa Muntoni, Salvatore Lecca, Valentina Satta, Antonio Luchicchi, Marco Pistis, Leigh V Panlilio, Liana Fattore, Steven R Goldberg, Walter Fratta, Paola Fadda

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Cannabis is the most commonly used illicit drug worldwide, and use is typically initiated during adolescence. The endocannabinoid system has an important role in formation of the nervous system, from very early development through adolescence. Cannabis exposure during this vulnerable period might lead to neurobiological changes that affect adult brain functions and increase the risk of cannabis use disorder. The aim of this study was to investigate whether exposure to Δ(9)-tetrahydrocannabinol (THC) in adolescent rats might enhance reinforcing effects of cannabinoids in adulthood. Male adolescent rats were treated with increasing doses of THC (or its vehicle) twice/day for 11 consecutive days (PND 45-55). When the animals reached adulthood, they were tested by allowing them to intravenously self-administer the cannabinoid CB1-receptor agonist WIN55,212-2. In a separate set of animals given the same THC (or vehicle) treatment regimen, electrophysiological and neurochemical experiments were performed to assess possible modifications of the mesolimbic dopaminergic system, which is critically involved in cannabinoid-induced reward. Behavioral data showed that acquisition of WIN55,212-2 self-administration was enhanced in THC-exposed rats relative to vehicle-exposed controls. Neurophysiological data showed that THC-exposed rats displayed a reduced capacity for WIN55,212-2 to stimulate firing of dopamine neurons in the ventral tegmental area and to increase dopamine levels in the nucleus accumbens shell. These findings-that early, passive exposure to THC can produce lasting alterations of the reward system of the brain and subsequently increase cannabinoid self-administration in adulthood-suggest a mechanism by which adolescent cannabis exposure could increase the risk of subsequent cannabis dependence in humans.

Original languageEnglish
Pages (from-to)1416-26
Number of pages11
JournalNeuropsychopharmacology
Volume41
Issue number5
DOIs
Publication statusPublished - Apr 2016
Externally publishedYes

Cite this

Scherma, Maria ; Dessì, Christian ; Muntoni, Anna Lisa ; Lecca, Salvatore ; Satta, Valentina ; Luchicchi, Antonio ; Pistis, Marco ; Panlilio, Leigh V ; Fattore, Liana ; Goldberg, Steven R ; Fratta, Walter ; Fadda, Paola. / Adolescent Δ(9)-Tetrahydrocannabinol Exposure Alters WIN55,212-2 Self-Administration in Adult Rats. In: Neuropsychopharmacology. 2016 ; Vol. 41, No. 5. pp. 1416-26.
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abstract = "Cannabis is the most commonly used illicit drug worldwide, and use is typically initiated during adolescence. The endocannabinoid system has an important role in formation of the nervous system, from very early development through adolescence. Cannabis exposure during this vulnerable period might lead to neurobiological changes that affect adult brain functions and increase the risk of cannabis use disorder. The aim of this study was to investigate whether exposure to Δ(9)-tetrahydrocannabinol (THC) in adolescent rats might enhance reinforcing effects of cannabinoids in adulthood. Male adolescent rats were treated with increasing doses of THC (or its vehicle) twice/day for 11 consecutive days (PND 45-55). When the animals reached adulthood, they were tested by allowing them to intravenously self-administer the cannabinoid CB1-receptor agonist WIN55,212-2. In a separate set of animals given the same THC (or vehicle) treatment regimen, electrophysiological and neurochemical experiments were performed to assess possible modifications of the mesolimbic dopaminergic system, which is critically involved in cannabinoid-induced reward. Behavioral data showed that acquisition of WIN55,212-2 self-administration was enhanced in THC-exposed rats relative to vehicle-exposed controls. Neurophysiological data showed that THC-exposed rats displayed a reduced capacity for WIN55,212-2 to stimulate firing of dopamine neurons in the ventral tegmental area and to increase dopamine levels in the nucleus accumbens shell. These findings-that early, passive exposure to THC can produce lasting alterations of the reward system of the brain and subsequently increase cannabinoid self-administration in adulthood-suggest a mechanism by which adolescent cannabis exposure could increase the risk of subsequent cannabis dependence in humans.",
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Scherma, M, Dessì, C, Muntoni, AL, Lecca, S, Satta, V, Luchicchi, A, Pistis, M, Panlilio, LV, Fattore, L, Goldberg, SR, Fratta, W & Fadda, P 2016, 'Adolescent Δ(9)-Tetrahydrocannabinol Exposure Alters WIN55,212-2 Self-Administration in Adult Rats' Neuropsychopharmacology, vol. 41, no. 5, pp. 1416-26. https://doi.org/10.1038/npp.2015.295

Adolescent Δ(9)-Tetrahydrocannabinol Exposure Alters WIN55,212-2 Self-Administration in Adult Rats. / Scherma, Maria; Dessì, Christian; Muntoni, Anna Lisa; Lecca, Salvatore; Satta, Valentina; Luchicchi, Antonio; Pistis, Marco; Panlilio, Leigh V; Fattore, Liana; Goldberg, Steven R; Fratta, Walter; Fadda, Paola.

In: Neuropsychopharmacology, Vol. 41, No. 5, 04.2016, p. 1416-26.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Adolescent Δ(9)-Tetrahydrocannabinol Exposure Alters WIN55,212-2 Self-Administration in Adult Rats

AU - Scherma, Maria

AU - Dessì, Christian

AU - Muntoni, Anna Lisa

AU - Lecca, Salvatore

AU - Satta, Valentina

AU - Luchicchi, Antonio

AU - Pistis, Marco

AU - Panlilio, Leigh V

AU - Fattore, Liana

AU - Goldberg, Steven R

AU - Fratta, Walter

AU - Fadda, Paola

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AB - Cannabis is the most commonly used illicit drug worldwide, and use is typically initiated during adolescence. The endocannabinoid system has an important role in formation of the nervous system, from very early development through adolescence. Cannabis exposure during this vulnerable period might lead to neurobiological changes that affect adult brain functions and increase the risk of cannabis use disorder. The aim of this study was to investigate whether exposure to Δ(9)-tetrahydrocannabinol (THC) in adolescent rats might enhance reinforcing effects of cannabinoids in adulthood. Male adolescent rats were treated with increasing doses of THC (or its vehicle) twice/day for 11 consecutive days (PND 45-55). When the animals reached adulthood, they were tested by allowing them to intravenously self-administer the cannabinoid CB1-receptor agonist WIN55,212-2. In a separate set of animals given the same THC (or vehicle) treatment regimen, electrophysiological and neurochemical experiments were performed to assess possible modifications of the mesolimbic dopaminergic system, which is critically involved in cannabinoid-induced reward. Behavioral data showed that acquisition of WIN55,212-2 self-administration was enhanced in THC-exposed rats relative to vehicle-exposed controls. Neurophysiological data showed that THC-exposed rats displayed a reduced capacity for WIN55,212-2 to stimulate firing of dopamine neurons in the ventral tegmental area and to increase dopamine levels in the nucleus accumbens shell. These findings-that early, passive exposure to THC can produce lasting alterations of the reward system of the brain and subsequently increase cannabinoid self-administration in adulthood-suggest a mechanism by which adolescent cannabis exposure could increase the risk of subsequent cannabis dependence in humans.

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KW - Behavior, Animal

KW - Benzoxazines

KW - Dopamine

KW - Dopaminergic Neurons

KW - Dronabinol

KW - Male

KW - Morpholines

KW - Naphthalenes

KW - Nucleus Accumbens

KW - Rats

KW - Receptor, Cannabinoid, CB1

KW - Self Administration

KW - Ventral Tegmental Area

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

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DO - 10.1038/npp.2015.295

M3 - Article

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EP - 1426

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

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ER -