Methamphetamine facilitates ethanol-induced depressions in cerebellar Purkinje neurons of prazocin- or DSP4-treated rats.
Methamphetamine (MA) and ethanol (EtOH) are two commonly abused drugs. Previous behavioral studies indicated that MA may synergistically alter EtOH responses. In the present study, we found that local application of MA did not potentiate ethanol-induced depressions of the spontaneous activity of Purkinje neurons in urethane-anesthetized rats. We and others previously found that, in cerebellar Purkinje neurons, EtOH and gamma-amino-butyric acid (GABA)-mediated depressions can be enhanced by norepinephrine (NE) acting via beta-adrenergic receptors while these responses are decreased by activation of alpha-adrenergic receptors. In the present experiment, after blocking alpha-adrenergic receptors with prazocin, MA significantly enhanced EtOH responses in most of neurons studied. It has been reported that MA may directly and indirectly enhance alpha-adrenergic and beta-adrenergic receptor-mediated responses. The present study may suggest that MA can negatively modulate (antagonize) the depressant effects of ethanol via the alpha-adrenergic receptor, which oppose the positive modulatory mechanism (potentiation of EtOH depression) via actions of the beta-adrenergic receptors. We found that lesioning NE neurons with N-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4), a selective noradrenergic neurotoxin, enhance the MA-facilitated ethanol responses, suggesting that this action of MA may not require NE. Since it has been reported that MA increases serotonin (5-HT) and catecholamine release from their nerve terminals, MA may potentiate EtOH depressions by facilitating the release of NE and 5-HT. Taken together, our data suggested that MA may modulate EtOH responses via catecholaminergic and serotonergic mechanisms in cerebellar Purkinje neurons.
Wang
Y
Y
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
Jeng
C H
CH
Lin
J C
JC
Wang
J Y
JY
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects*; D003863:Depression / Q000139:chemically induced*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013566:Sympathomimetics / Q000494:pharmacology
D001596:Benzylamines; D013566:Sympathomimetics; D000431:Ethanol; D008694:Methamphetamine; C012102:DSP 4; D011224:Prazosin