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Ethanol self-administration is regulated by CB1 receptors in the nucleus accumbens and ventral tegmental area in alcohol-preferring AA rats.
Alcohol Clin Exp Res. 2008 Nov; 32(11):1976-83.AC

Abstract

BACKGROUND

Endogenous cannabinoids and their receptors, CB1 receptors in particular, have been implicated in mediation of ethanol reinforcement. Previously, suppression of ethanol drinking by CB1 antagonists has been demonstrated in many experimental paradigms. However, the exact mechanism by which CB1 antagonists modulate ethanol drinking remains elusive. In the present study, we assessed the role of CB1 receptors within the key regions of the mesolimbic dopamine pathway, the nucleus accumbens (NAcc) and ventral tegmental area (VTA), in regulation of ethanol self-administration.

METHODS

Adult male alcohol-prefer AA rats were trained to self-administer either 10% (w/v) ethanol or 0.1% (w/v) saccharin under an FR1 schedule during daily 30-minute sessions. Following stable baseline responding, rats were tested after systemic administration of the CB1 antagonist SR141716A (0 to 10 mg/kg) and the agonist WIN55,212-2 (0 to 2 mg/kg). Separate groups of rats were implanted with bilateral cannulas aimed at the NAcc or VTA, and tested after microinjections of SR141716A (0 to 3 microg) and WIN55,212-2 (0 to 5 microg) into the NAcc or VTA. The highest intracerebral doses were tested also in rats responding for a 0.1% saccharin solution.

RESULTS

SR141617A dose-dependently suppressed ethanol responding after systemic administration. Microinjections of SR141617A both into NAcc and VTA attenuated ethanol responding. In addition, intra-NAcc injections of SR141617A suppressed saccharin intake. Although low doses of systemically given WIN55,212-2 increased ethanol responding, no effects were seen after WIN55,212-2 microinjections into NAcc or VTA.

CONCLUSIONS

Bidirectional changes in ethanol self-administration by the systematically administered CB1 agonist and antagonist show that ethanol reinforcement is controlled by CB1 receptors in alcohol-preferring AA rats. Replication of the suppressive effects by CB1 antagonism in the NAcc and VTA suggests that endocannabinoids and their receptors mediate ethanol reinforcement through interaction with the mesolimbic dopamine pathway.

Authors+Show Affiliations

National Public Heath Institute, Department of Mental Health and Alcohol Research, Helsinki, Finland.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18782338

Citation

Malinen, Hanna, and Petri Hyytiä. "Ethanol Self-administration Is Regulated By CB1 Receptors in the Nucleus Accumbens and Ventral Tegmental Area in Alcohol-preferring AA Rats." Alcoholism, Clinical and Experimental Research, vol. 32, no. 11, 2008, pp. 1976-83.
Malinen H, Hyytiä P. Ethanol self-administration is regulated by CB1 receptors in the nucleus accumbens and ventral tegmental area in alcohol-preferring AA rats. Alcohol Clin Exp Res. 2008;32(11):1976-83.
Malinen, H., & Hyytiä, P. (2008). Ethanol self-administration is regulated by CB1 receptors in the nucleus accumbens and ventral tegmental area in alcohol-preferring AA rats. Alcoholism, Clinical and Experimental Research, 32(11), 1976-83. https://doi.org/10.1111/j.1530-0277.2008.00786.x
Malinen H, Hyytiä P. Ethanol Self-administration Is Regulated By CB1 Receptors in the Nucleus Accumbens and Ventral Tegmental Area in Alcohol-preferring AA Rats. Alcohol Clin Exp Res. 2008;32(11):1976-83. PubMed PMID: 18782338.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethanol self-administration is regulated by CB1 receptors in the nucleus accumbens and ventral tegmental area in alcohol-preferring AA rats. AU - Malinen,Hanna, AU - Hyytiä,Petri, Y1 - 2008/09/06/ PY - 2008/9/11/pubmed PY - 2009/2/10/medline PY - 2008/9/11/entrez SP - 1976 EP - 83 JF - Alcoholism, clinical and experimental research JO - Alcohol Clin Exp Res VL - 32 IS - 11 N2 - BACKGROUND: Endogenous cannabinoids and their receptors, CB1 receptors in particular, have been implicated in mediation of ethanol reinforcement. Previously, suppression of ethanol drinking by CB1 antagonists has been demonstrated in many experimental paradigms. However, the exact mechanism by which CB1 antagonists modulate ethanol drinking remains elusive. In the present study, we assessed the role of CB1 receptors within the key regions of the mesolimbic dopamine pathway, the nucleus accumbens (NAcc) and ventral tegmental area (VTA), in regulation of ethanol self-administration. METHODS: Adult male alcohol-prefer AA rats were trained to self-administer either 10% (w/v) ethanol or 0.1% (w/v) saccharin under an FR1 schedule during daily 30-minute sessions. Following stable baseline responding, rats were tested after systemic administration of the CB1 antagonist SR141716A (0 to 10 mg/kg) and the agonist WIN55,212-2 (0 to 2 mg/kg). Separate groups of rats were implanted with bilateral cannulas aimed at the NAcc or VTA, and tested after microinjections of SR141716A (0 to 3 microg) and WIN55,212-2 (0 to 5 microg) into the NAcc or VTA. The highest intracerebral doses were tested also in rats responding for a 0.1% saccharin solution. RESULTS: SR141617A dose-dependently suppressed ethanol responding after systemic administration. Microinjections of SR141617A both into NAcc and VTA attenuated ethanol responding. In addition, intra-NAcc injections of SR141617A suppressed saccharin intake. Although low doses of systemically given WIN55,212-2 increased ethanol responding, no effects were seen after WIN55,212-2 microinjections into NAcc or VTA. CONCLUSIONS: Bidirectional changes in ethanol self-administration by the systematically administered CB1 agonist and antagonist show that ethanol reinforcement is controlled by CB1 receptors in alcohol-preferring AA rats. Replication of the suppressive effects by CB1 antagonism in the NAcc and VTA suggests that endocannabinoids and their receptors mediate ethanol reinforcement through interaction with the mesolimbic dopamine pathway. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/18782338/Ethanol_self_administration_is_regulated_by_CB1_receptors_in_the_nucleus_accumbens_and_ventral_tegmental_area_in_alcohol_preferring_AA_rats_ L2 - https://doi.org/10.1111/j.1530-0277.2008.00786.x DB - PRIME DP - Unbound Medicine ER -