No abstract

Repeated exposure to nicotine increases both the number of central nicotinic receptors and the behavioral stimulant effect of nicotine. In the present experiments, the behavioral response to nicotine was examined in photocell activity cages. Groups of rats were tested using doses from 0.1 to 1.6 mg/kg both before and after all rats were exposed for 5 days to a common dose of 0.2 mg/kg/day. Prior to the 5-day exposure, there was a dose-related stimulant response to nicotine, with a maximum response seen at 0.4 mg/kg. After the 5-day exposure, the dose-effect curve was shifted upward, so that greater stimulation was produced at each test dose of nicotine. Other groups of rats were exposed for 5 days to doses of nicotine ranging from 0.01 to 0.30 mg/kg/day. On the 6th day all rats received a common test dose of 0.2 mg/kg and their response was measured in the activity cages. In animals exposed to 0.01 mg/kg/day, the test day response was not different from saline controls, but the groups exposed to higher doses showed increased stimulation in response to the common test dose. Measurements of nicotinic receptor binding using [3H]-acetylcholine found increased binding in groups receiving 0.03 mg/kg/day or more, but not in the group that received 0.01 mg/kg/day. The correspondence between the doses that increase behavioral stimulant reactions to nicotine and the doses that increase nicotinic binding suggest that increased receptor numbers may be responsible for the increased behavioral stimulation. However, rats given high doses (1.6 mg/kg, twice per day) did not show increased behavioral stimulation to a test dose of 0.2 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

Single-unit recordings of nucleus accumbens septi (NAS) neurons in halothane-anesthetized rats revealed that microinfusions of morphine into the ventral tegmental area (VTA) primarily inhibited spontaneously active NAS units. These inhibitory effects were reversed by alpha-flupenthixol (s.c.), suggesting a role for dopamine (DA) in the observed opiate-induced effect. VTA opiate microinfusions also inhibited the evoked (driven) responses of silent cells (spontaneously inactive) in the NAS elicited by stimulation of hippocampal afferents to the NAS. In addition, this inhibition of driven response was reversed by naloxone (s.c.) but not by alpha-flupenthixol, implying a VTA-mediated non-DA mechanism. Morphine applied iontophoretically to cells within the NAS inhibited spontaneous activity but not fimbria-driven cellular activity, suggesting that the systemic effects of opiates on NAS activity can be mediated directly in the NAS as well as through VTA afferents. Moreover, since VTA-induced inhibition of fimbria-driven activity was reversed by systemic opiates, opiates also can exert effects through other, as yet unidentified NAS afferent systems.