Chronic haloperidol administration increases GABA binding and enhances neuronal responsiveness to iontophoresed GABA in rat globus pallidus.
Experiments were conducted to assess the effects of chronic haloperidol (CHAL) administration on gamma-aminobutyric acid (GABA) receptor binding within the rat globus pallidus (GP) and on the responsiveness of individual pallidal neurons to microiontophoretically applied GABA and glycine. Rats were administered haloperidol in their food for 30 days in increasing concentrations and the experiments were conducted 2 days after termination of the haloperidol treatment. GABA receptor binding and neuronal responsiveness to GABA were significantly increased within the GP following CHAL treatment. The mean EC50 value for GABA was significantly decreased in the CHAL-treated rats, but there was no change in the EC50 for glycine. Scatchard analysis of [3H]muscimol binding demonstrated a single high-affinity binding site (Kd = 5 nM) within both control and CHAL-treated rats. The binding capacity (Bmax) of this high-affinity site was significantly increased in CHAL-treated rats without any change in the dissociation constant (Kd) for this site. These results suggest that CHAL administration may lead to a decrease in GABA release by striatopallidal efferents. The results of this study, combined with those of our previous study on SNR neurons, have demonstrated that blockade of striatally mediated dopamine (DA) neurotransmission leads to similar changes in GABAergic mechanisms at the level of the GP and SNR and suggest that DA regulation of the striatopallidal and striatonigral GABAergic pathways need not be differentially organized as has previously been postulated.
Frey
J M
JM
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
Ticku
M K
MK
Bell
R D
RD
Huffman
R D
RD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005947:Glucose; D006220:Haloperidol; D005998:Glycine