THE EFFECT OF METHAMPHETAMINE ON THE RELEASE OF ACETYLCHOLINE IN THE RAT STRIATUM

We examined the effect of methamphetamine on the release of acetylchol ine in the striatum of freely moving rats, using an in vivo microdialy sis method. The basal level of acetylcholine was 3.67 +/- 0.47 pmol/30 mu l per 15 min in the presence of neostigmine (10 mu M). Tetrodotoxi n (1 mu M), a selective blocker of voltage-dependent Na+ channels, mar kedly inhibited the release of acetylcholine in the striatal perfusate s. Apomorphine (1.0 mg/kg, i.p.), a dopamine receptor agonist, also si gnificantly attenuated acetylcholine release. Methamphetamine (0.1 and 0.5 mg/kg, i.p.) did not immediately affect acetylcholine release in the striatum, but a dose of 1.0 mg/kg (i.p.) induced an increase of ac etylcholine release in the striatum at 15-60 min. Striatal infusion of methamphetamine (5 and 10 mu M) did not influence acetylcholine relea se. The increase following intraperitoneal administration of methamphe tamine was slightly diminished by haloperidol (0.5 mg/kg). After micro injection of the neurotoxin, 6-hydroxydopamine (6 mu g/3 mu l), in the substantia nigra 7 days before, the increase of acetylcholine induced by the administration of methamphetamine (1.0 mg/kg) was slightly att enuated, whereas the administration of reserpine (2 mg/kg, i.p.) 24 h before, combined with alpha-methyl-p-tyrosine (300 mg/kg, i.p.) 2.5 h before, completely blocked the increase in release of acetylcholine. T hese findings suggest that methamphetamine exerts an excitatory influe nce on striatal acetylcholine release in freely moving rats, and that this excitatory effect involves the dopaminergic system and the catech olaminergic system. (C) 1998 Elsevier Science B.V. All rights reserved .