The Electrically‐Stimulated Spinal Reflex in Pithed Rats: A Possible Test Model for Evaluating Blockade of Central Dopamine D1 and D2 Receptors

Abstract

Intravenous injection of the dopamine (DA) D1 receptor agonist SK&F 38393 (4.3 mumol/kg = 1.25 mg/kg), or the DA D2 receptor agonist pergolide (3.2 mumol/kg = 1.25 mg/kg) increased the electrically-stimulated spinal reflex in pithed rats by more than 600 per cent. The specific DA D1 receptor antagonist SCH 23390 potently inhibited the SK&F 38393-induced spinal reflex but not the pergolide-induced reflex. The DA D2 receptor antagonists clebopride and YM 09151-2 inhibited the pergolide-induced reflex only. Two mixed DA D1/D2 antagonists (cis(Z)-flupentixol and zuclopenthixol) inhibited the effects of both SK&F 38393 and pergolide on the spinal reflex, while the neuroleptically inactive isomer of clopenthixol (trans(E)-clopenthixol) was also inactive in this context. Various antagonists (prazosin (alpha 1), idazoxan (alpha 2), 1- propranolol (beta), bicuculline (GABA] were inactive in the test model. The 5-HT2 receptor antagonists altanserin and ketanserin also showed antagonistic effect. It is concluded that the electrically-stimulated spinal reflex in pithed rats can be used as a test model to estimate the blockade of central DA D1 and DA D2 receptors without influence from alpha 1-adrenergic, alpha 2-adrenergic, beta-adrenergic and GABA-ergic receptors. However, a serotonergic receptor antagonism does influence the specificity of the test model.