Pain‐related depression of intracranial self‐stimulation in rats: effects of the delta opioid agonist SNC80 and the psychomotor stimulant cocaine

Abstract

Pain is associated with a stimulation of some behaviors (e.g. withdrawal responses) and a depression of other behaviors (e.g. feeding, locomotion, responding maintained by many types of positive reinforcement). We have argued that analgesic drug development may benefit from complementary evaluation of drug effects on both pain‐stimulated and pain‐depressed behaviors. In this study, intraperitoneal injection of dilute lactic acid (1.8% in a volume of 1ml/kg) was used as a noxious stimulus in rats to stimulate a stretching response and to depress intracranial self‐stimulation (ICSS) of the medial forebrain bundle. The delta opioid agonist SNC80 (1–10 mg/kg, i.p.) dose‐dependently blocked both acid‐stimulated stretching and acid‐induced depression of ICSS without altering control ICSS in the absence of the noxious stimulus. In contrast, cocaine (1–10 mg/kg i.p.) blocked acid‐depressed ICSS only at doses that also facilitated control ICSS, and cocaine had no effect on acid‐stimulated stretching. Thus, the antinociceptive effects of SNC80 in the assay of pain‐depressed ICSS could be dissociated from the non‐selective stimulant effects of cocaine. Supported by NIH grants RO1‐DA11460 and R01‐NS070715.