NEttnOSCt [ LETTERS ELSEVIER Neuroscience Letters 168 (1994) 213 216 Alteration of pallidal cholinergic activity in MPTP-treated monkeys: effect of dihydro-a-ergocryptine (DEK) D. Curti*, E. Izzo, G. Benzi Institute of Pharmacology, Faculty of Sciences, University of Pavia, 27100 Pavia, Italy Received 14 April 1993; Revised version received 20 December 1993: Accepted 23 December 1993 Abstract Monkeys, intravenously administered with MPTP at the dose of 0.3 mg/kg for 5 consecutive days, develop a severe Parkinson-like syndrome. Cholinergic enzyme activities are increased in the internal segment of the globns pallidus (GPi) and into a lesser extent in the external globus pallidus (GPe). Cholinergic activities are not significantly affected in the caudate and putamen nor in the frontal, parietotemporal, occipital cortices and in the cerebellum. The treatment of the animals twice daily for 2 weeks with dihydro-c~-ergocryptine (DEK) starting 5 days before the first MPTP administration counteracts the neurotoxin-induced alteration in the internal pallidum and ameliorates some motor related parkinsonian symptoms. Key words: Monkey; MPTP; Parkinsonism; Cholinergic activity; Dihydro-c~-ergocryptine; Globus pallidus The neurotoxin 1-methyl-4-phenyl-l,2,3,6-tetrahy- dropyridine (MPTP) induces Parkinson (PD)-like symp- toms in human and non-human primates [4,12]. MPTP is converted by the monoamino oxidase type B (MAO-B) to MPP + (1-methyl-4-phenylpyridine) which is taken up by the dopamine (DA) carrier, accumulates intraneu- ronally and rather selectively destroys the dopaminergic neurons in the pars compacta of the substantia nigra (SNc) causing a marked decrease of the DA content in the caudate and putamen nuclei [4]. The neostriatum is the site where the DA-acetylcholine (Ach) interaction are reported to occur principally. The prevailing opinion (although there is no general agreement [6]) is that the DA released from nigro-striatal terminals tonically in- hibits, through stimulation of O 2 receptors, the release of Ach from striatal cholinergic interneurons [15,27]. D 2 receptors antagonists remove this inhibitory modulation and increase Ach release in the striatum [28]. Central dopaminergic and cholinergic systems seem to exert a mutual inverse relationship [1]; however, the effect of nigrostriatal denervation on cholinergic activity outside *Corresponding author. Fax: (39) 382-386 385. 0304-3940/94157.00 © 1994 Elsevier Science Ireland Ltd. All rights reserved SSDI 0304-3940(94)00008-X the neostriatum is not understood and it is likely to play a role in Parkinson's-associated motor disturbances; in fact cholinergic stimulation of GPi elicits rigidity of the paravertebral musculature and increases tremor ampli- tude in PD patients [5]. The aim of this investigation was to evaluate in some striatal and extrastriatal brain regions the short term consequences of MPTP administration on the choliner- gic enzymes (choline acetyltransferase, CHAT, and ace- tylcholinesterase, AchE) and on pyruvate dehydrogenase complex (PDHc) which catalyzes the oxidative decar- boxylation of pyruvate to acetylcoenzyme A, linking cholinergic and energy metabolism. A treatment with dihydro-a-ergocryptine (DEK), a D2 receptor agonist, was also performed. This ergot derivative improves motor performances (rigidity, bradykinesia and tremor) in PD patients [21]. Male cynomolgus monkeys were housed at the primate facility of the Istituto di Ricerche Biomediche 'Antoine Marxer' RBM (Ivrea, Italy). Animal care and handling were in accordance with fundamental principles by CIOMS and with provisions of EEC Council Directive 86-609. The animals were randomly divided into three groups: MPTP-treated animals (n = 6) received a dose of