γ-Aminobutyric acid type B receptor changes in the rat striatum and substantia nigra following intrastriatal quinolinic acid lesions.

Abstract

Changes in the regional distribution of the metabotropic GABA type B receptors (GABA(B)) were investigated in a rat model of Huntington's disease. Animals received a unilateral intrastriatal injection of quinolinic acid (QA), and GABA(B) immunoreactivity was monitored 3, 11, and 21 days postinjection in the striatum and substantia nigra (SN). Two antibodies, recognizing either the GABA(B1) or the GABA(B2) receptor subtypes, were used. QA injection rapidly induced a protracted increase in GABA(B1) or GABA(B2) immunoreactivity in the lesioned striatum, despite the neuronal loss. In the SN, a continuous increase in GABA(B1) and GABA(B2) immunoreactivity was observed at all time points in the ipsilateral pars reticulata (SNr), whereas the pars compacta (SNc) was unaffected by this phenomenon. This increase was supported by a densitometric analysis. At day 21 postlesion induction, intensely labeled stellate cells and processes were found in the ipsilateral SNr, in addition to immunoreactive neurons. Double labeling of GABA(B1) and glial fibrillary acidic protein (GFAP) showed that the stellate cells were reactive astrocytes. Hence, part of the sustained increase in GABA(B) immunoreactivity that takes place in the SNr and possibly the striatum may be ascribed to reactive astrocytes. It is suggested that GABA(B) receptors are up-regulated in these reactive astrocytes and that agonists might influence the extent of this astroglial reaction.