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Keywords:

  • Akinesia;
  • CP-93129;
  • GABA;
  • globus pallidus;
  • 5HT1B receptor;
  • reserpine;
  • 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