Abstract
Cocaine inhibits the 5-HT 2-mediated (±)-DOI-induced head-twitch response (HTR) in mice in a dose-dependent manner. In order to investigate the possible inhibitory mechanism(s) of cocaine on 5-HT 2 receptor function, we studied the effects of the selective adrenergic α 2 receptor antagonist yohimbine and the β-adrenergic/5-HT 1 receptor antagonist alprenolol, and the 5-HT 3 antagonist ICS 205–930 on the inhibitory action of cocaine on the (±)-DOI-induced HTR. Neither yohimbine (0.1 and 0.5 mg/kg) nor alprenolol (10 mg/kg) pretreatment had any significant effect on the (±)-DOI-induced HTR. However, both antagonists prevented the inhibitory effects of cocaine on the (±)-DOI-induced HTR. The 5-HT 3 antagonist ICS 205–930 neither produced HTR nor decreased the (±)-DOI-induced HTR frequency. The present results suggest that cocaine inhibits 5-HT 2 receptor function by increasing the synaptic concentration of norepinephrine and serotonin via inhibition of their uptake and thus indirectly stimulating the respective inhibitory adrenergic α 2 and serotonergic 5-HT 1A receptors. Furthermore, cocaine's 5-HT 3 antagonist properties appear not to play a role in the inhibition of head-twitch behavior.
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