Changes in locomotion and dopamine neurotransmission following amphetamine, haloperidol, and exposure to novel environmental stimuli

Abstract

Locomotor behavior and dopamine (DA) neurotransmission were assessed in rats exposed to either a novel or familiar stimulus environment while under the influence of amphetamine, haloperidol or saline. The behavioral results indicated that, as expected, amphetamine increased horizontal locomotor activity in a dose-dependent manner. Exposure to novelty also increased horizontal activity, and this behavioral effect was disrupted by both amphetamine and haloperidol. Regardless of whether the animals were exposed to the novel or familiar stimulus environment, amphetamine increased DA synthesis in the nigrostriatal system, but not in the mesolimbic system, whereas haloperidol increased DA synthesis in both the nigrostriatal and mesolimbic systems. Amphetamine also decreased DA metabolism and haloperidol increased DA metabolism in both the nigrostriatal and mesolimbic systems. In contrast, exposure to novelty alone was without effect on DA synthesis or metabolism in any region examined, suggesting that novelty-induced hyperactivity and amphetamine-induced hyperactivity involve different neurochemical mechanisms. However, exposure to novelty while under the influence of haloperidol produced a significant increase in DA metabolism in both the nigrostriatal and mesolimbic systems. These latter results suggest that exposure to novelty may produce a measurable activation of DA systems when the autoreceptors involved in the negative feedback loop are blocked.