Calcium channel blockade interacts with a neuroleptic to attenuate the conditioning of amphetamine's behavioral effects in the rat

Conditioned responses to drug-related cues appear to be related to the maintenance of stimulant addiction. These conditioned responses are not blocked by treatments that block the direct effects of stimulants and may contribute to the high rate of relapse of addicts. Rats administered (+)- amphetamine in a specific environment exhibit conditioned locomotion when subsequently palced in that environment without drugs. The neuroleptic haloperidol significantly attenuated amphetamine-induced locomotor activity but failed to reduce conditioned locomotion. Nimodipine, an l-type calcium channel antagonist, had no effect on amphetamine-induced unconditioned or conditioned locomotion. However, combined nimodipine and haloperidol treatment blocked the unconditioned and attenuated the conditioned locomotor response to amphetamine. Conjunctive therapy with nimodipine and haloperidol may provide an efficacious treatment for stimulant addiction. In addition, nimodipine may provide an important adjunctive therapy for schizophrenia, allowing the use of lower doses of neuroleptic to avoid extrapyramidal side effects.