Effects of 5,7-dihydroxytryptamine lesions of the nucleus accumbens on rat intravenous morphine self-administration

Abstract

The role of serotonergic innervations of the nucleus accumbens in the processes maintaining intravenous morphine self-administration were assessed. Pairs of male rat littermates were implanted with intravenous jugular catheters and bilateral injection guide cannulae into the central medial nucleus accumbens, made physically dependent on morphine and then allowed to intravenously self-administer with continuous access. When stable baselines of drug intake were obtained (2-3 weeks), one of each pair received bilateral microinjections of vehicle and the other 5,7-dihydroxytryptamine (5,7-DHT) into the nucleus accumbens. Response independent infusions of morphine were delivered for 24 hours at the previous rate of self-injection and the animals were again allowed to self-administer while drug intake was monitored for thirteen days. The littermate pairs were then sacrificed by immersion in liquid nitrogen, the brains removed at -20 degrees C and frozen sections of the cannulae tract taken for histological assessment. The nucleus accumbens, anterior caudate nucleus and pyriform cortex were removed at -20 degrees C and biogenic monoamine content determined. The 5,7-DHT lesions resulted in a significant increase in drug intake and significantly decreased the content of serotonin (5-HT) and 5-hydroxyindoleacetic acid in the nucleus accumbens (-49% and -30%, respectively) and 5-HT in the anterior caudate nucleus (-14%) and pyriform cortex (-17%). Dose-effect relationships were assessed in four additional animals before and after similar bilateral 5,7-DHT lesions.(ABSTRACT TRUNCATED AT 250 WORDS)