Differential effects of proglumide on mesolimbic and nigrostriatal dopamine function.

Cholecystokinin octapeptide (CCK-8) is prevalent as a co-transmitter in the mesolimbic dopamine pathway. The effect of proglumide, a CCK-8 antagonist, on two acute and one chronic behavioral models of dopamine function was tested. First, haloperidol was used to inhibit stereotypies induced by apomorphine in rats. Pre-administration of proglumide significantly shifted the haloperidol dose response curve to the left. Second, rats were injected in the left caudate nucleus with kainic acid. Three weeks later, haloperidol was used to inhibit apomorphine-induced circling. Pre-administration of proglumide had no effect on this haloperidol dose response curve. Third, either proglumide, haloperidol, or combined treatment was administered to rats for 2 weeks. In proglumide-treated animals, a significant increase in 3H-spiperone binding sites in the nucleus accumbens was observed.