Interactions between intra-perifornical region sulpiride and intra-ventral tegmental area AP5 on measures of locomotor activity and conditioned place preference

Abstract

 Infusions of sulpiride, a dopamine D₂/D₃ receptor antagonist within the perifornical region of the lateral hypothalamus have been shown previously to exhibit a behavioural profile generally attributed specifically to activation of the mesoaccumbens dopamine projection. Experiment 1 confirmed previous work showing that repeated homecage pretreatment with sulpiride (5 μg) in the perifornical region of the lateral hypothalamus 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 mesoaccumbens dopamine projection via the ventral tegmental area. Thus, repeated intra-perifornical infusions with sulpiride were without effect initially, but resulted in a gradual increase in locomotor activity during subsequent sessions. Intra-ventral tegmental area infusions of the NMDA receptor antagonist AP5 (0.3, 1.0 nmol) were without intrinsic effect upon locomotor activity at any time. However, AP5 blocked the ability of repeated sulpiride infusions to increase locomotor activity, and the ability of intra-perifornical sulpiride to support the acquisition of a conditioned place preference. AP5-sulpiride co-infusions also increased locomotor activity in a non-incremental manner. These data suggest there to be a functionally significant projection from the perifornical region of the lateral hypothalamus to the ventral tegmental area in the control over locomotor activity and rewarded behaviour.