The 5HT1B receptor agonist, CP-93129, inhibits [3H]-GABA release from rat globus pallidus slices and reverses akinesia following intrapallidal injection in the reserpine-treated rat
Article first published online: 29 JAN 2009
2000 British Pharmacological Society
British Journal of Pharmacology
Volume 130, Issue 8, pages 1927–1932, August 2000
How to Cite
Chadha, A., Sur, C., Atack, J. and Duty, S. (2000), The 5HT1B receptor agonist, CP-93129, inhibits [3H]-GABA release from rat globus pallidus slices and reverses akinesia following intrapallidal injection in the reserpine-treated rat. British Journal of Pharmacology, 130: 1927–1932. doi: 10.1038/sj.bjp.0703526
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received February 15, 2000, Revised May 30, 2000, Accepted June 8, 2000)
- globus pallidus;
- 5HT1B receptor;
- Parkinson's disease
This study examined whether activation of 5HT1B receptors in the rodent globus pallidus (GP) could reduce GABA release in vitro and reverse reserpine-induced akinesia in vivo.
Microdissected slices of GP from male Sprague Dawley rats (300–350 g) were preloaded with [3H]-GABA. During subsequent superfusion, 4 min fractions were collected for analysis of release. The effects of the 5HT1B receptor agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP-93129), on 25 mM KCl-evoked release were examined using a standard dual stimulation paradigm.
Male Sprague Dawley rats (270–290 g), stereotaxically cannulated above the GP, were rendered akinetic by injection of reserpine (5 mg kg−1 s.c.). Eighteen hours later, the rotational behaviour induced by unilateral injection of CP-93129 was examined.
CP-93129 (0.6–16.2 μM) produced a concentration-dependent inhibition of 25 mM KCl-evoked [3H]-GABA release reaching a maximum inhibition of 52.5±4.5%. The effect of a submaximal concentration of CP-93129 (5.4 μM) was fully inhibited by the 5HT1B receptor antagonist, isamoltane (10 μM).
Following intrapallidal injection, CP-93129 (30–330 nmol in 0.5 μl) produced a dose-dependent increase in net contraversive rotations reaching a maximum of 197±32 rotations in 240 min at 330 nmol. Pre-treatment with isamoltane (10 nmol in 1 μl) inhibited the effects of a submaximal dose of CP-93129 (220 nmol) by 84±6%.
These data suggest that at least some 5HT1B receptor function as heteroreceptors in the GP, reducing the release of GABA. Moreover, CP-93129-mediated activation of these receptors in the GP provides relief of akinesia in the reserpine-treated rat model of PD.
British Journal of Pharmacology (2000) 130, 1927–1932; doi:10.1038/sj.bjp.0703526