Chronic neuroleptic treatment and mesolimbic dopamine denervation induce behavioural supersensitivity to opiates

In the present study the functional relationship between enkephalinergic and dopaminergic neurones at the level of the nucleus accumbens was investigated. The study consisted of two experiments in which dopaminergic (DA) transmission was chronically inhibited, and the behavioural locomotor response to intra-accumbens opiate injections analysed. First, specific 6-OHDA lesion of the DA-A10 neurones (either in nucleus accumbens or ventral tegmental area) was found markedly to increase the behavioural excitatory effects induced by nucleus accumbens injection of opioid peptides or morphine. Specific lesion of the central noradrenergic neurones had no such effect. Second, chronic pharmacological blockade of DA activity either with reserpine or a neuroleptic (pipothiazine palmitate) similarly induced a strong enhancement of the behavioral response to intra-accumbens opiate injection. The results are discussed in terms of novel mechanisms underlying denervation supersensitivity, and may have important implications for the relation between dopamine dysfunction in mental illness and opiate addiction.