Morphine withdrawal produces differential effects on the rate of lever-pressing for brain self-stimulation in the hypothalamus and midbrain in rats

Abstract

Rats were implanted with stimulating electrodes either in the medial forebrain bundle-lateral hypothalamus (MFB-LH) or the midbrain-central gray area (MID-CG), and were trained to lever-press for electrical brain self-stimulation (ICSS). The animals were made tolerant to morphine (15 mg/kg) by twice daily injections for a four-day period. Withdrawal was then induced either by substituting saline (spontaneous withdrawal) or by administering naloxone (1.0 mg/kg) (precipitated withdrawal). Changes in body weight, in the incidence of diarrhea, and in the rates of lever-pressing for ICSS were recorded during the five-day withdrawal period. In both the MFB-LH implanted and the MID-CG implanted groups, the duration and magnitude of changes in lever-pressing were greater when withdrawal was precipitated than when it was spontaneous. Independently of the type of withdrawal, however, the behavioral disruption was greater for animals implanted in the MFB-LH than for animals implanted in the MID-CG. The changes in body weight were similar for both electrode sites and both types of withdrawal. Diarrhea only occurred in the precipatated withdrawal group and its incidence was similar for animals implantedin the two sites. Three additional groups of animals were implanted in the MFB-LH, made tolerant to morphine, and given naloxone as above. They were administered clonidine (10, 30 or 100 μg/kg) 30 min prior to naloxone to attenuate the effects of withdrawal. The 30 μg/kg dose of clonidine produced maximal attenuation of the disruption in lever-pressing. None of the doses of clonidine attenuated weight loss, but all three doses reduced the incidence of diarrhea. The ICSS procedure demonstrated that the behavior during withdrawal can be related to the brain area that is stimulated.