Pergamon 0361-9230(94)00198-7 BrainResearchBulletin, Vol. 36, No. 3, pp. 241-249, 1995 Copyright© 1994Elsevier Science Ltd Printedin the USA.All rightsreserved 0361-9230/95$9.50 + .00 Responses of Forebrain Neurons to the MAO-B Blocker L-Deprenyl A. CZURK0,* B. FALUDI,* Z. KARADI,* I. VIDA,* CS. NIEDETZKY,* J. KNOLL1- AND L. LI~NARD .1 *Neurophysiology Research Group of the Hungarian Academy of Sciences at the Institute of Physiology, Pecs University, Medical School, H-7643 Pecs, Szigeti St. 12, Hungary tDepartment of Pharmacology, Semmelweis University Medical School, H-1089 Budapest, Hungary [Received 15 November 1993; Accepted 27 July 1994] ABSTRACT: Despite the large amount of neuropharmacological data concerning catecholamine (CA) mechanisms of the mare- malian brain, little is known yet about the effects of MAO-inhib- itors on single neurons. The present series of experiments aim to elucidate these specific neuruchemical attributes of forebrain cells. Single neuron activity was recorded by means of multi- barreled microelectrodes in the caudate nucleus, globus palli- dus, and amygdala of both anesthetized rats and anesthetized or alert monkeys during microelectrophoretic application of the MAO-B blocker L-deprenyl (DEPR). CAs (doparnine and noradren- aline), glutamate, GABA, and acetylcholine were also applied. Nearly the half (46%) of all forebrain neurons tested responded, exclusively with inhibition, to DEPR, and the CA-sensibve cells were especially responsive to the MAO-B inhibitor. The time course of DEPR-induced neuronal suppression was shorL In some cases, amphetamine (AMPH) and clorgyline (CLOR) were also applied microelectrophoretically. AMPH elicited similar ac- Uvity changes to Umse seen after DEPR administra'dons, whereas CLOR applications were less effective. Our results provide evi- dence that DEPR can effectively modulate the activity of CA-sen- sitive neurons in the three different forebrain regions of two different species. On the basis of this data, the possible neuro- chemical mechanisms of DEPR action are discussed. KEY WORDS: Single neuron recording, Microelectrophoresis, L-Deprenyl, Catecholamines, Caudate nucleus, Globus pallidus, Amygdala, Rat, Monkey. INTRODUCTION L-Deprenyl (DEPR) is an irreversible monoamine oxidase-B (MAO-B) inhibitor [19,20,25]. It is highly preferred in clinical studies involving parkinsonian patients because, in the human brain, dopamine (DA) is known to be metabolized mainly by MAO-B. DEPR was originally used in combination with levo- dopa, the cornerstone of the treatment of Parkinson's disease (PD), because DEPR has been demonstrated to potentiate and prolong the efficacy of levodopa therapy [3,5,11,32]. In recent years, several clinical tests were carried out to investigate the efficacy of DEPR as a primary treatment in PD. It has been shown that DEPR monotherapy can be a good initial treatment in PD [1,27,35,36,45,46]. Separate studies have also demonstrated that DEPR can be a useful and reliable tool for the treatment of another severe neu- rological disorder, the dementia of Alzheimer's type (DAT). DEPR improved cognitive functions and reduced behavioral al- terations without severe side effects in Alzheimer patients [26,34,41 ]. Although it is known that DEPR is a specific inhibitor of MAO-B, its neurochemical action, even in the case of the exten- sively examined PD, is not clear. It is considered that DEPR decreases the MAO-B activity, originating predominantly from glial cells, and so it can facilitate DA neurotransmission and en- hances the dopaminergic tone in the human brain [11,19,20,42]. The clinical benefits of DEPR, however, could not be associated only with the MAO-B inhibition because DEPR has other im- portant effects as well [21,22,24]. DEPR is a potent and revers- ible inhibitor of the uptake of amines into nerve endings of CA neurons [19,20], and its major metabolites are (-) methamphet- amine and (-) amphetamine that stimulate the release of CAs [17,20,38]. Furthermore, the inhibition of MAO-B results in a rapid accumulation of 2-phenylethylamin (PEA), known to po- tentiate the DA neurotransmission [39], and last but not least, DEPR has neuroprotective effects [11,43,44] that could explain the slow progression of parkinsonian symptoms after DEPR treatment [1,2,27,32,35]. Despite the large amount of neuropharmacological data on CA mechanisms of this MAO blocker, little is known about the effects of DEPR on single neurons. In the present study, there- fore, single neuron activity was extracellularly recorded from forebrain areas innervated by the ascending CA systems. These systems have been reported to be involved in the development of parkinsonian-like symptoms (such as sensory-perceptual and motor deficits) [12-14,28,30] and they could also have func- tional role in the pathology of DAT [8]. Recordings were made by means of carbon fiber multibarreled glass microelectrodes, and DEPR and other chemicals were applied microelectrophor- etically to each isolated neuron. The main question was whether DEPR had any detectable influence on the firing of forebrain neurons. In both anesthetized rats and monkeys and in alert mon- keys, recordings were performed in the a) caudate nucleus (CN) b) globus pallidus (GP), and c) amygdaloid body (AMY). AI- To whom requests for reprints should be addressed. 241