Pharmacological inhibition of DA- and 5-HT activity blocks spontaneous and cocaine-activated behavior: reversal by chronic cocaine treatment

Abstract

Recently it was shown that the combined pretreatment with low autoreceptor preferring dose levels of apomorphine (0.05 mg/kg) and 8-OHDPAT (0.05 mg/kg), which decrease dopaminergic and serotonergic activity, induces a profound behavioral inhibition and also blocks the stimulant effects of cocaine. In two experiments, we report that the acute blockade of spontaneous and cocaine locomotor stimulant effects by pretreatment with 8-OHDPAT (0.05 mg/kg) plus apomorphine (0.05 mg/kg) is dose-dependently (0.0 2.5, 5.0, and 10.0 mg/kg cocaine) reversed with repeated cocaine treatments. Using a paired vs. unpaired Pavlovian conditioning protocol, we found that this reversal by cocaine (10 mg/kg) of the inhibition by the combined 8-OHDPAT plus apomorphine pretreatment occurred for the paired but not the unpaired cocaine treatment. The findings suggest that this reversal of behavioral inhibition is mediated by the transformation of the drug cues generated by 8-OHDPAT and apomorphine into cocaine-conditioned stimuli which can activate behavior.