Fos-like immunoreactivity in tyrosine hydroxylase and substance P-like immunoreactive neurones 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-containing neurones have been implicated in reward. In the present study twocolour immunohistochemistry was used to investigate whether Fos protein was induced in dopaminergic (tyrosine hydroxylase) and substance P-containing neurones of guinea-pig brain following intracerebroventricular 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 study has shown that of the large number of neurones showing Fos-like immunoreactivity following a single injection of morphine or U50,488H, few were tyrosine hydroxylase-positive (dopaminergic) but a larger number were substance Plike immunoreactive. These results support the proposal that substance P plays a role in reward and reinforcement.