Changes in GABAB RECEPTOR mRNA expression in the rodent basal ganglia and thalamus following lesion of the nigrostriatal pathway
Section snippets
Production of 6-OHDA or sham lesions of the nigrostriatal tract
All procedures were carried out in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and all efforts were made to keep animal suffering and the number of animals used to a minimum. Male, Sprague–Dawley rats (Tucks, Southend-on-Sea, UK) weighing 250–270 g were housed in a light- (12-h light/dark cycle) and humidity-controlled environment with free access to food and water. Thirty minutes prior to surgery animals were dosed with pargyline (5 mg kg−1 i.p.) and desipramine (25 mg kg
Lesion verification
In the 6-OHDA-lesioned group, six of the animals produced at least four rotations/min−1 consistent with a >90% lesion of the nigrostriatal tract (Hefti et al., 1980). In these animals, net contraversive rotations were significantly greater at 188±21 rotations 30 min−1 than those obtained in sham-lesioned rats (4±1 rotations 30 min−1).
Effective loss (99.9±0.1% reduction in lesion compared with the control side; P<0.05) of [3H]-mazindol binding to striatal dopaminergic terminals was observed in
Distribution of GABAB receptor mRNA in the BG and thalamus
All of the GABAB receptor mRNA species examined showed relatively widespread distribution throughout the BG and thalamus. The pattern of gene expression noted for the GABAB(2) subunit was consistent with previous reports, showing a characteristic absence of mRNA within the striatum and NAcb and highest levels within the thalamus Durkin et al., 1999, Clark et al., 2000. The data obtained here are concordant with those of Liang et al. (2000), showing highest levels of GABAB(1a) mRNA expression in
Acknowledgements
This research was funded by the British Pharmacological Society and the Parkinson's Disease Society. T. Johnston was funded by an A. J. Clark Studentship from the British Pharmacological Society.
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