INTERACTIONS BETWEEN INTRA-PERIFORNICAL REGION SULPIRIDE AND INTRA-VENTRAL TEGMENTAL AREA AP5 ON MEASURES OF LOCOMOTOR-ACTIVITY AND CONDITIONED PLACE PREFERENCE

Infusions of sulpiride, a dopamine D-2/D-3 receptor antagonist within the perifornical region of the lateral hypothalamus have been shown pr eviously to exhibit a behavioural profile generally attributed specifi cally to activation of the mesoaccumbens dopamine projection. Experime nt 1 confirmed previous work showing that repeated homecage pretreatme nt with sulpiride (5 mu g) in the perifornical region of the lateral h ypothalamus resulted subsequently in an enhanced locomotor response to a d-amphetamine challenge. Experiment 2 examined the possibility that the observed behavioural changes were due to stimulation of the mesoa ccumbens dopamine projection via the ventral tegmental area. Thus, rep eated intra-perifornical infusions with sulpiride were without effect initially, but resulted in a gradual increase in locomotor activity du ring subsequent sessions. Intra-ventral tegmental area infusions of th e NMDA receptor antagonist AP5 (0.3, 1.0 nmol) were without intrinsic effect upon locomotor activity at any time. However, AP5 blocked the a bility of repeated sulpiride infusions to increase locomotor activity, and the ability of intra-perifornical sulpiride to support the acquis ition of a conditioned place preference. AP5-sulpiride co-infusions al so increased locomotor activity in a non-incremental manner. These dat a suggest there to be a functionally significant projection from the p erifornical region of the lateral hypothalamus to the ventral tegmenta l area in the control over locomotor activity and rewarded behaviour.