Effects of psychotomimetic and antipsychotic agents on neocortical and striatal concentrations of various amino acids in the rat.
A subcutaneous injection of small and moderate doses (1.6, 3.2, 4.0 and 4.8 mg/kg) of the schizophrenomimetic methamphetamine caused a dose-related increase in the tissue content (the net content) of L-Arg and L-Asn in the neocortex and striatum at 60 min, but not at 360 min, after injection. The methamphetamine-induced (4.8 mg/kg) increases in levels of these amino acids were significantly attenuated by pretreatment with an antipsychotic drug, haloperidol (1 mg/kg) or clozapine (10 mg/kg). In the neocortex, a clozapine-reversible increase in the level of L-Thr was also observed 60 min after methamphetamine administration. Striatal concentrations of L-Glu, L-Ser, LThr, Gly and L-Ala were augmented by the same regimen in a haloperidol- and clozapine-sensitive fashion. A moderate dose of another schizophrenomimetic phencyclidine (7.5 mg/kg) given subcutaneously induced robust abnormal behavior, a diminution in the neocortical and striatal levels of L-Asp and an increase in the striatal L-Ala content without significant effects on the other amino acids studied. These results suggest that neocortical and striatal L-Arg, L-Asn, L-Thr, Gly, L-Ala or L-Ser may be implicated in the psychotomimetic effects of methamphetamine and might display mutual interaction with cerebral dopaminergic transmission. The differential effects of methamphetamine and phencyclidine on the net neocortical and striatal concentrations of various amino acids might, at least in part, underlie the distinct features of psychoses induced by these two drugs.
Sakurai
Shin-ichiro
S
Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
Ishii
Sumikazu
S
Umino
Asami
A
Shimazu
Dai
D
Yamamoto
Naoki
N
Nishikawa
Toru
T
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000494:pharmacology; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000596:Amino Acids; D014150:Antipsychotic Agents; D008694:Methamphetamine; D006899:Mixed Function Oxygenases; C069781:pentachlorophenol monooxygenase; D003024:Clozapine; D006220:Haloperidol