Abstract
Subsensitivity to γ-aminobutyric acid (GABA) agonists was sought in rats treated 1 or 4 weeks with flurazepam (FZP). Sensitivity to GABA and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) was assessed by measuring contralateral rotation following unilateral microinjection of drug into the substantia nigra pars reticulata (SNpr). Immediately and 48 h after chronic treatment GABA, 200 μg or THIP, 60 ng was infused into SNpr. Immediately, but not 48 h after 1 week of FZP treatment, GABA subsensitivity was shown by a significantly reduced total number of contralateral turns and peak rotation rare. There was no change in the response to THIP after 1 week FZP treatment. Following 4 week FZP treatment, no subsensitivity to GABA or THIP was evident. Previous results showed subsensitivity to muscimol after 4, but not 1 week of FZP treatment. Since muscimol and THIP are not subject to uptake, there may be increased uptake of GABA after 1 week of FZP treatment, though it may not persist during continued treatment. Differential regulation of GABA agonist effects in SNpr may be related to their acting at differing GABA A receptor subpopulations, and variable responses of these subpopulations to chronic BZ treatment.
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