Clozapine and haloperidol have differential effects on glutamic acid decarboxylase mRNA in the pallidal nuclei of the rat.
The striatum, and one of its targets, the pallidum (globus pallidus and entopeduncular nucleus) are based ganglia nuclei involved in extrapyramidal movement control. Gamma-aminobutyric acid (GABA)ergic neurons of the pallidum may be important for the expression of the effects of agents which alter striatal neurotransmission. In this study, rats were treated once daily for 28 days with either haloperidol or clozapine, two drugs which respectively, do and do not, induce extrapyramidal movement disorders. In situ hybridization histochemistry was used to quantify the levels of labeling for the messenger ribonucleic acid encoding glutamic acid decarboxylase, the main synthesizing enzyme for GABA in neurons of the striatum, globus pallidus, and entopeduncular nucleus. Neither drug treatment altered levels of labeling in the striatum. Haloperidol treatment increased the level of labeling in the entopeduncular nucleus and clozapine treatment increased labeling in the globus pallidus suggesting that these drugs exert different regulatory effects on pallidal neurons.
Mercugliano
M
M
Department of Pharmacology, University of Pennsylvania, Philadelphia.
Saller
C F
CF
Salama
A I
AI
U'Prichard
D C
DC
Chesselet
M F
MF
D000818:Animals; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005917:Globus Pallidus / Q000187:drug effects* / Q000201:enzymology; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D005968:Glutamate Decarboxylase; D003024:Clozapine; D006220:Haloperidol