Chronic flupentixol treatment potentiates the reinforcing properties of systemic heroin administration

Data show that chronic dopamine (DA) receptor blockade produces a marked increase in the sensitivity to the reinforcing and discriminative stimulus properties of systemic heroin administration and that this increase is not attributable to heroin-induced locomotor activation.

Abstract

The behavioral effects of systemic heroin administration were examined in rats subjected to flupentixol impregnation prior to and during behavioral testing. In the first experiment, the dose of heroin required to produce a place preference was determined in two groups of rats, one of which had received chronic flupentixol decanoate (12 mg/kg, sc, every 10 days for 6 weeks) and the other which had received the palm oil vehicle during the same time period. It was found that whereas 60 micrograms/kg of heroin was required to produce a place preference in control rats, only 7.5 micrograms/kg was sufficient to do so in chronic neuroleptic-treated rats. In a second experiment, the locomotor activating effect of heroin was evaluated in two groups of rats that had been subjected to the same chronic regimen as in Experiment 1. Locomotor activity was enhanced in both groups following 120 micrograms/kg heroin, whereas 30 micrograms/kg was ineffective in either group. Finally, it was found that neuroleptic-treated, but not control, rats rapidly learned to self-administer intravenous infusions of an unusually low dose of heroin (4 micrograms) and to discriminate these infusions from vehicle infusions. Together, these data show that chronic dopamine (DA) receptor blockade produces a marked increase in the sensitivity to the reinforcing and discriminative stimulus properties of systemic heroin administration and that this increase is not attributable to heroin-induced locomotor activation. The results are discussed in terms of the role of DA systems in opiate reinforcement processes.