Intraaccumbens administration of NMDA receptor antagonist (+/-)-CPP prevents locomotor activation conditioned by morphine and amphetamine in rats.

In the present experiments the influence of NMDA receptor antagonist (+/-)-CPP on morphine- and amphetamine-conditioned activation of locomotor activity was studied in rats chronically implanted with bilateral cannulas in the nucleus accumbens septi. Animals were conditioned by pairing subcutaneous injections of morphine (3.0 mg/kg), amphetamine (1.5 mg/kg), or saline with a distinctive environment. Following the five drug-environment pairings, rats displayed significant increase in locomotion when exposed to the drug-paired environment. The expression of this conditioned response was completely prevented by the bilateral intraaccumbens pretreatment with (+/-)-CPP (1.0, but not 0.1 or 0.3 microgram/ microliter/side). These findings suggest that the locomotor hyperactivity conditioned by morphine and amphetamine involves the activation of NMDA receptors within the nucleus accumbens.