CHOLINERGIC INHIBITION OF SELF-STIMULATION BEHAVIOR

¹ Michigan Neuropsychopharmacology Research Program, Department of Pharmacology, University of Michigan, Ann Arbor, Michigan

The purpose of this study was to determine the effects of two acetylcholinesterase (AChE) inhibitors, physostigmine and neostigmine, on self-stimulation behavior in the rat and to correlate their behavioral effects with total brain acetyicholine (ACh) and AChE. The effects of equimolar doses of physostigmine and neostigmine were compared after s.c. injection. Adult Holtzman male rats were implanted with chronic bipolar electrodes in the hypothalamus for optimal seIf-stimulation behavior. Physostigmine was much more effective than neostigmine in depressing self-stimulation. An increase in brain ACh and a decrease in AChE were obtained after physostigmine, which correlated with behavioral depressant effects. Similar findings were not observed with equimolar doses of neostigmine, indicating that the latter does not penetrate readily into the brain to affect this behavior. Even large doses of neostigmine which depressed self-stimulation did not cause an increase in brain ACh or a lowering of AChE, suggesting that this depression was due to a peripheral mechanism. It is concluded that in rats central cholinergic neuronal systems are involved in inhibiting the self-stimulation of the hypothalamus with an electrical current.

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