Effects of intracerebroventricular administration of methyl naloxonium chloride on heroin self-administration in the rat.

A quaternary derivative of naloxone, methyl naloxonium chloride (MN), was administered intracerebroventricularly (ICV) to rats trained to self-administer heroin intravenously. MN produced a dose-dependent (0.5-4.0 micrograms) increase in responding for heroin. Since MN is unlikely to reach the peripheral circulation in these doses, these results were viewed as strongly supporting the hypothesis that central opiate receptors are solely responsible for mediating the reinforcing properties of heroin during self-administration. In addition, the present study suggests that intracerebral MN injections may prove to be a useful technique in the search for central substrates of heroin reward.