Low doses of methylnaloxonium in the nucleus accumbens antagonize hyperactivity induced by heroin in the rat.

The effect of microinjection of a quaternary opiate antagonist methylnaloxonium (MN) in the lateral ventricle, ventral tegmental area (VTA) and nucleus accumbens (N.Acc.) was examined on the locomotor activation produced by a subcutaneous heroin injection (0.5 mg/kg) in the rat. At this dose heroin typically produced an initial depressant phase (0-30 min) followed by a prolonged hyperactivity (40-120 min). Lateral ventricular injections did not significantly reverse the initial depressant effects of heroin (0-30 min), and a dose of 4 micrograms was needed to reverse the subsequent hyperactivity (40-120 min). The most potent blockade was observed following injections into the N.Acc. where 0.1 microgram significantly reversed the initial depressant effects of heroin (0-30 min), and 0.25 microgram significantly reversed the subsequent hyperactivity (40-120 min). In the VTA, MN had the weakest effects, failing to reverse significantly the initial depressant effects of heroin (0-30 min), and only attenuating the subsequent hyperactivity at the highest doses. It is suggested that certain opiates act on the mesolimbic dopaminergic pathway at the level of the cell bodies in the VTA, but more critically in the N.Acc., possibly on opiate receptors postsynaptic to the dopamine neurons.