Effects of single and repeated phencyclidine administration on [3H]flunitrazepam binding in rat brain.
Repeated administration of phencyclidine (PCP) induces behavioral sensitization to dopaminergic neural transmission. This phenomenon has been implicated in the pathophysiology of schizophrenia. Recently, GABAergic agonists have been shown to reduce behavioral activity induced by enhanced dopaminergic neural transmission, which is mediated by the GABA(A)/benzodiazepine (BZD) receptor complex. Thus, to investigate the role of BZD receptors during induction and expression of behavioral sensitization in PCP-sensitized animals, the effects of both single and repeated PCP administration on BZD receptors in rat brain were examined using in vitro quantitative autoradiography. Repeated PCP administration failed to significantly alter levels of [3H]flunitrazepam (FNZ) binding in any of the regions examined. However, significant increases in levels of [3H]FNZ binding were found in the nucleus accumbens and ventral pallidum 1 h after single administration of PCP. These results suggest that BZD binding sites may not play important roles in the development of PCP-induced sensitization at several sites of GABA(A)/BZD receptor complex, while changes in GABA function in the nucleus accumbens differ from other areas following single administration of N-methyl-D-aspartate (NMDA) antagonist.
Abe
Shuzo
S
Department of Psychiatry, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Suzuki
Toshihito
T
Endo
Kenichi
K
Hori
Takafumi
T
Arai
Heii
H
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005445:Flunitrazepam / Q000378:metabolism*; D018757:GABA Modulators / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D005445:Flunitrazepam; D010622:Phencyclidine