GABAergic supersensitivity within the pars reticulata of the rat substantia nigra following chronic haloperidol administration.
These studies were performed to evaluate the effects of chronic haloperidol administration on the responsiveness of the pars reticulata neurons of the substantia nigra (SNR) to microiontophoretically applied gamma-aminobutyric acid (GABA) and glycine. Rats were administered haloperidol in their feed (CHAL treatment) for 30 days in increasing concentrations. All experiments were conducted two days after termination of the CHAL treatment. GABA receptor binding and neuronal responsiveness to GABA were significantly increased within the SNR following CHAL treatment. The mean EC50 value for GABA was significantly decreased for SNR neurons in CHAL-treated rats, but there was no change in the EC50 for glycine. Specific [3H]GABA binding (4 nM) was elevated by more than 50% within the SNR. Scatchard analysis of [3H]muscimol binding data revealed that the binding capacities (Bmax) of both high and low affinity GABA binding sites within the SNR were significantly increased without a change in the apparent dissociation constants (Kd) of either site. Although no regional difference in responsiveness to GABA was detected within the SNR of CHAL-treated rats, the spontaneous activity of neurons located within the rostral two-thirds of the nucleus was reduced; however, there was no change in spontaneous activity of neurons located within the caudal one-third. These data provide direct physiological evidence to support the conclusion that the increase in GABA binding within the SNR following CHAL treatment reflects a neuronal supersensitivity to GABA.
Department of Pharmacology, University of Texas Health Science Center at San Antonio, TX 78284-7764.
J M
JM
Frey
M K
MK
Ticku
R D
RD
Huffman
D000818:Animals; D005998:Glycine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D006220:Haloperidol; D005998:Glycine