FOS-LIKE IMMUNOREACTIVITY IN TYROSINE-HYDROXYLASE AND SUBSTANCE P-LIKE IMMUNOREACTIVE NEURONS IN GUINEA-PIG BRAIN FOLLOWING INTRACEREBROVENTRICULAR INJECTION OF MORPHINE AND U50,488H

Opioid drugs such as morphine have powerful reinforcing effects which lead to drug-seeking behaviour. Both dopamine- and substance P-contain ing neurones have been implicated in reward. In the present study two- colour immunohistochemistry was used to investigate whether Fos protei n was induced in dopaminergic (tyrosine hydroxylase) and substance P-c ontaining neurones of guinea-pig brain following intracerebroventricul ar administration of the predominantly mu-receptor agonist, morphine, and the kappa-receptor agonist, U50,488H, which have been reported to produce rewarding and aversive effects, respectively. The present stud y has shown that of the large number of neurones showing Fos-like immu noreactivity following a single injection of morphine or U50,488H, few were tyrosine hydroxylase-positive (dopaminergic) but a larger number were substance P-like immunoreactive. These results support the propo sal that substance P plays a role in reward and reinforcement.