Conclusions
These data provide the first evidence that NAC 5-HT(2A) and 5-HT(2C) receptors are critical for the expression of cocaine-induced neuroplasticity following protracted withdrawal, which has relevance for their therapeutic utility in the treatment of addiction.
Methods
The effects of intra-NAC infusions of the 5-HT(2A) antagonist R-(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine methanol (MDL 100907; 0, 50, 100, 500 nM) or the 5-HT(2C) antagonist [6-chloro-5-methyl-1-(6-(2-methylpiridin-3-yloxy)pyridine-3-yl carbamoyl] inodoline dihydrochloride (SB 242084; 0, 50, 100, 500 nM) were first assessed upon the expression of locomotor activity elicited by a 15-mg/kg cocaine challenge injection administered at 3-week withdrawal. A follow-up in vivo microdialysis experiment then compared the effects of the local perfusion of 0, 50, or 100 nM of each antagonist upon cocaine-induced dopamine and glutamate sensitization in the NAC.
Results
Although neither MDL 100907 nor SB 242084 altered acute cocaine-induced locomotion, SB 242084 reduced acute cocaine-elevated NAC dopamine and glutamate levels. Intra-NAC perfusion with either compound blocked the expression of cocaine-induced locomotor and glutamate sensitization, but only MDL 100907 pretreatment prevented the expression of cocaine-induced dopamine sensitization. Conclusions: These data provide the first evidence that NAC 5-HT(2A) and 5-HT(2C) receptors are critical for the expression of cocaine-induced neuroplasticity following protracted withdrawal, which has relevance for their therapeutic utility in the treatment of addiction.