Cross sensitization between phencyclidine and methamphetamine: II repeated administration of methamphetamine at a high dose

We investigated whether effects of phencyclidine (PCP) were modified by repeated pretreatment with methamphetamine (MAP) at a high (15mg/kg/day for 4 days) dose in rats. The incidence of turning, head-weaving and backpedalling induced by PCP was increased by pretreatment with MAP. In the rats pre-treated with MAP, 1) behavioral responses induced by acute MAP, apomorphine and 5-methoxy-N,N-dimethyltryptamine were potentiated; 2) dopamine content in the striatum, nucleus accumbens and frontal cortex and serotonin content in the striatum and frontal cortex were decreased; and 3) the Bmax and Kd values for [³H]-spiperone and [³H]-ketanserin bindings to brain synaptic membrane were significantly increased. These results suggest that 4 days-repeated administration of MAP (15 mg/kg) increases postsynaptic activity of both dopaminergic and serotonergic neuronal systems, and that there may be cross sensitization to PCP in the dopaminergic neuronal function following repeated administration of MAP at high dose.