Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors

被引:135
作者
Gewirtz, JC
Marek, GJ
机构
[1] Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, Dept Psychiat, New Haven, CT 06508 USA
[2] Abraham Ribicoff Res Facil, New Haven, CT 06508 USA
关键词
phenethylamines; hallucinogens; serotonin; mGlu2/3; receptors; head shakes; DOI; 5-HT2A receptors; LY354740;
D O I
10.1016/S0893-133X(00)00136-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Recent electrophysiological studies in our laboratory have demonstrated a physiological interaction between 5-HT2A and metabotropic glutamate2/3 (mGlu2/3) receptors in the medial prefrontal cortex. Several behavioral studies have found that phenethylamine hallucinogens with partial agonist activity at 5-HT2A receptors induce head shakes when directly administered into Me medial prefrontal cortex. The purpose of Me present experiments was to examine whether an interaction occurs between mGlu2/3 and 5-HT2A receptors on a behavioral level using head shakes induced by phenethylamine hallucinogens as a model of 5-HT2A receptor activation. Administration of the mGlu2/3 agonist LY354740 (0.3-10 mg/kg, ip) suppressed head shakes induced by the phenethylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Conversely, administration of the mGlu2/3 antagonist LY342495 (1 mg/kg, ip) enhanced the frequency of DOI-induced head shakes. Taken together, these results raise the possibility that the psychomimetic properties of hallucinogenic drugs maybe mediated in part, via increased glutamate release following activation of 5-HT2A receptors. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
引用
收藏
页码:569 / 576
页数:8
相关论文
共 74 条
[11]   CORRESPONDENCE BETWEEN 5-HT2 RECEPTORS AND SEROTONERGIC AXONS IN RAT NEOCORTEX [J].
BLUE, ME ;
YAGALOFF, KA ;
MAMOUNAS, LA ;
HARTIG, PR ;
MOLLIVER, ME .
BRAIN RESEARCH, 1988, 453 (1-2) :315-328
[12]   BUPRENORPHINE TREATMENT OF REFRACTORY DEPRESSION [J].
BODKIN, JA ;
ZORNBERG, GL ;
LUKAS, SE ;
COLE, JO .
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, 1995, 15 (01) :49-57
[13]   SEROTONIN2 AGONIST ADMINISTRATION DOWN-REGULATES RAT-BRAIN SEROTONIN2 RECEPTORS [J].
BUCKHOLTZ, NS ;
ZHOU, DF ;
FREEDMAN, DX .
LIFE SCIENCES, 1988, 42 (24) :2439-2445
[14]   OPIUM AS A TRANQUILIZER [J].
CARLSON, ET ;
SIMPSON, MM .
AMERICAN JOURNAL OF PSYCHIATRY, 1963, 120 (02) :112-&
[15]  
Cartmell J, 1999, J PHARMACOL EXP THER, V291, P161
[16]   EFFECT OF SEROTONIN ANTAGONISM IN SCHIZOPHRENIA - A PILOT-STUDY WITH SETOPERONE [J].
CEULEMANS, DLS ;
GELDERS, YG ;
HOPPENBROUWERS, MLJA ;
REYNTJENS, AJM ;
JANSSEN, PAJ .
PSYCHOPHARMACOLOGY, 1985, 85 (03) :329-332
[17]   THE HEAD-TWITCH RESPONSE TO INTRAPERITONEAL INJECTION OF 5-HYDROXYTRYPTOPHAN IN THE RAT - ANTAGONIST EFFECTS OF PURPORTED 5-HYDROXYTRYPTAMINE ANTAGONISTS AND OF PIRENPERONE, AN LSD ANTAGONIST [J].
COLPAERT, FC ;
JANSSEN, PAJ .
NEUROPHARMACOLOGY, 1983, 22 (08) :993-1000
[18]  
COLPAERT FC, 1982, J PHARMACOL EXP THER, V221, P206
[19]   MORPHINE AS AN ANTIPSYCHOTIC [J].
COMFORT, A .
CLINICAL TOXICOLOGY, 1977, 11 (04) :383-386
[20]   Pharmacology and functions of metabotropic glutamate receptors [J].
Conn, PJ ;
Pin, JP .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1997, 37 :205-237