Dopamine-acetylcholine interaction in the rat lateral hypothalamus in the control of locomotion

Abstract

Pharmacological, neurochemical, and behavioral techniques were used to characterize DA-ACh interaction within the lateral hypothalamus (LH) in the context of locomotion, feeding behavior, and reinforcement. In Experiment 1, the muscarinic agonist carbachol injected in the LH increased locomotor activity in proportion to dose. In Experiment 2, the same doses of carbachol proportionately increased exctracellular DA in the nucleus accumbens (Nac) as monitored by brain microdialysis. Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) also increased. In Experiment 3, LH infusion by reverse microdialysis of the D(2) receptor blocker sulpiride released ACh in the LH in a dose-response manner. This suggested that sulpiride disinhibits ACh release via D(2) receptors in the LH and thereby facilitates behavior. Confirming this in Experiment 4, local LH atropine 5 min before sulpiride suppressed the locomotor response to sulpiride for about 20 min. These results suggest that sulpiride acts in the LH by disinhibiting a hypothalamic locomotor mechanism that is cholinergically driven and connected with the mesoaccumbens dopamine pathway. Given prior results that local sulpiride in the LH can induce hyperphagia and reward, this system may be involved in searching for food and rewarding feeding behavior. In conclusion, DA acts in the LH via D(2) receptors to inhibit cholinergic neurons or terminals that are part of an approach system for eating.