Relationship between gnawing compulsion and central dopaminergic mechanism in guinea pigs

Abstract

It has been reported that an increase in dopaminergic activity in the striatum can induce gnawing compulsion, a stereotyped behavior. Apomorphine, amphetamine and L-DOPA also produce such effects, particularly in the rat. However, it has been reported that the gnawing compulsion in the guinea pig cannot be induced with L-DOPA and is not related to the levels of catecholamine in the brain. It is of essential importance in this kind of research to clarify whether or not a dopaminergic mechanism is equally involved in gnawing compulsion of the rodent in general. The present study dealt with the mechanism of gnawing compulsion with L-DOPA administration to guinea pigs. Gnawing compulsion was amplified by crystal pick-up and amplifiers and was continuously recorded by an inkwriting-oscilloscope. The recorded data were scored for quantitative and objective analysis. Certainly, L-DOPA alone did not induce continuous gnawing, but the gnawing was obviously induced by pretreatment with benserazide, a peripheral decarboxylase inhibitor. The induced gnawing compulsion was inhibited by pimozide and haloperidol which are both dopamine receptor blockers. When catecholamine synthesis was inhibited by pretreatment with α-methyl-p-tyrosine, the amphetamine induced gnawing compulsion alone was markedly inhibited, but the apomorphine or L-DOPA induced gnawing compulsion following the pretreatment with benserazide was not inhibited. Therefore, it was deduced that gnawing compulsion was induced with amphetamine indirectly by dopamine release, with apomorphine by its direct stimulation of the dopamine receptor, and with L-DOPA by its action on the dopamine ieceptor, after having been converted to dopamine. Based on these results, it was concluded that the dopaminergic mechanism is closely involved in gnawing compulsion seen in the guinea pig as well as in the rat.