Pharmacological analysis of analgesia and self-stimulation elicited by electrical stimulation of catecholamine nuclei in the rat brain.

The relationship between intracranial self-stimulation (ICSS) and stimulation-produced analgesia (SPA) was investigated in that rat employing an operant bar-press response and a modification of the hot-plate test. ICSS and SPA were elicited through bipolar electrodes chronically implanted in two catecholamine nuclei; the nucleus locus coeruleus (LC) and the substantia nigra (SN). These sites have previously been shown to yield both phenomena. SPA was shown to be of a magnitude similar to that of morphine. In addition, SPA deriving from both LC and SN was significantly reversed by the specific opiate antagonist, naloxone. The intensity of the stimulating current sufficient to induce SPA was found to be higher than that required for ICSS. The pharmacological susceptibilities of the two phenomena were tested by administering a number of drugs: haloperidol, propranolol, pimozide and AMPT attenuated ICSS in both LC and SN, while leaving SPA unaffected. In contrast, methysergide and PCPA blocked SPA and simultaneously facilitated ICSS. The present results indicate a dissociation of ICSS and SPA from LC and SN at both physiological and neurochemical levels; ICSS rates appeared to be a function of catecholaminergic tone, while SPA depended upon the integrity of serotonin transmission.