RATIONALE: Several lines of evidence indicate that the endogenous cannabinoid system is involved in the pharmacological and behavioural effects of alcohol. The mesolimbic dopaminergic (DA) system and the nucleus accumbens (NAc) process rewarding properties of drugs of abuse, including alcohol and cannabinoids, whereas endocannabinoids in these regions modulate synaptic function and mediate short- and long-term forms of synaptic plasticity. OBJECTIVES: The present study was designed to investigate the contribution of the endogenous cannabinoid system in alcohol electrophysiological effects in the mesolimbic reward circuit. METHODS: We utilized extracellular single cell recordings from ventral tegmental area (VTA) DA and NAc neurons in anesthetized rats. DA neurons were antidromically identified as projecting to the shell of NAc, whereas NAc putative medium spiny neurons were identified by their evoked responses to basolateral amygdala (BLA) stimulation. RESULTS: Alcohol stimulated firing rate of VTA DA neurons and inhibited BLA-evoked NAc neuron spiking responses. The cannabinoid type-1 receptor (CB1) antagonist rimonabant (SR141716A) fully antagonized alcohol effect in both regions. In the NAc, either inhibition of the major catabolic enzyme of the endocannabinoid anandamide, the fatty-acid amyd hydrolase, with URB597 or a pretreatment with the CB1 receptor agonist WIN55212-2 significantly depressed alcohol-induced effects in the NAc. CONCLUSIONS: These results corroborate the notion of the involvement of endocannabinoids and their receptors in the actions of alcohol and highlight the endocannabinoid system as a valuable target in the therapy for alcoholism.
RATIONALE: Several lines of evidence indicate that the endogenous cannabinoid system is involved in the pharmacological and behavioural effects of alcohol. The mesolimbic dopaminergic (DA) system and the nucleus accumbens (NAc) process rewarding properties of drugs of abuse, including alcohol and cannabinoids, whereas endocannabinoids in these regions modulate synaptic function and mediate short- and long-term forms of synaptic plasticity. OBJECTIVES: The present study was designed to investigate the contribution of the endogenous cannabinoid system in alcohol electrophysiological effects in the mesolimbic reward circuit. METHODS: We utilized extracellular single cell recordings from ventral tegmental area (VTA) DA and NAc neurons in anesthetized rats. DA neurons were antidromically identified as projecting to the shell of NAc, whereas NAc putative medium spiny neurons were identified by their evoked responses to basolateral amygdala (BLA) stimulation. RESULTS:Alcohol stimulated firing rate of VTA DA neurons and inhibited BLA-evoked NAc neuron spiking responses. The cannabinoid type-1 receptor (CB1) antagonist rimonabant (SR141716A) fully antagonized alcohol effect in both regions. In the NAc, either inhibition of the major catabolic enzyme of the endocannabinoid anandamide, the fatty-acid amyd hydrolase, with URB597 or a pretreatment with the CB1 receptor agonist WIN55212-2 significantly depressed alcohol-induced effects in the NAc. CONCLUSIONS: These results corroborate the notion of the involvement of endocannabinoids and their receptors in the actions of alcohol and highlight the endocannabinoid system as a valuable target in the therapy for alcoholism.
Authors: Giancarlo Colombo; Salvatore Serra; Giovanni Vacca; Mauro A M Carai; Gian Luigi Gessa Journal: Pharmacol Biochem Behav Date: 2005-06 Impact factor: 3.533
Authors: Miriam Melis; Simona Perra; Anna Lisa Muntoni; Giuliano Pillolla; Beat Lutz; Giovanni Marsicano; Vincenzo Di Marzo; Gian Luigi Gessa; Marco Pistis Journal: J Neurosci Date: 2004-11-24 Impact factor: 6.167
Authors: Sheketha R Hauser; Simon N Katner; Robert A Waeiss; William A Truitt; Richard L Bell; William J McBride; Zachary A Rodd Journal: Pharmacol Biochem Behav Date: 2020-07-23 Impact factor: 3.533
Authors: Erik B Oleson; Michael V Beckert; Joshua T Morra; Carien S Lansink; Roger Cachope; Rehab A Abdullah; Amy L Loriaux; Dustin Schetters; Tommy Pattij; Mitchell F Roitman; Aron H Lichtman; Joseph F Cheer Journal: Neuron Date: 2012-01-26 Impact factor: 17.173