5-HT1A RECEPTORS AND THE TAIL-FLICK RESPONSE .5. OPPOSITE MODULATION OF 5-HT1A RECEPTOR-INDUCED SPONTANEOUS TAIL-FLICKS BY ALPHA(1A)-ADRENOCEPTOR AS COMPARED WITH ALPHA(2D)-ADRENOCEPTOR IN RAT LUMBAR SPINAL-CORD

Spontaneous tail-flicks (STFs) in the rat are mediated by postsynaptic serotonin (5-HT)(1A) receptors in lumbar spinal cord (Bervoets et al. , 1993). In this study, we examined the role of alpha(1)- as compared with alpha(2)-adrenoceptors in their modulation. STFs elicited by the 5-HT1A agonist 8-OH-DPAT were potently blocked by the alpha(1)-adrenoc eptor antagonist prazosin, as well as by WB 4101 and 5-methylurapidil, antagonists with a preference for the alpha(1A)-subtype of adrenocept or. In contrast, several alpha(2)-antagonists, for example, idazoxan a nd the preferential alpha(2D)-antagonist BRL 44408, (biphasically) pot entiated 8-OH-DPAT-induced STFs. Whereas STFs were unaffected by the a lpha(1)-adrenoceptor agonist cirazoline, they were blocked both by the alpha(2)-agonist UK 14,304 and by the preferential alpha(2D)-agonists guanfacine and guanabenz. The intrathecal administration onto lumbar spinal cord of prazosin or of the preferential alpha(1A)-antagonist be noxathian (which does not cross the blood-brain barrier) blocked STFs evoked by s.c. injection of 8-OH-DPAT. Intrathecal UK 14,304 acted sim ilarly. Conversely, STFs elicited by intrathecal 8-OH-DPAT were blocke d by s.c. prazosin or UK 14,304. Cirazoline and the preferential alpha (1A)-agonist methoxamine (which does not cross the blood-brain barrier ) elicited STFs upon intrathecal administration onto lumbar but not ce rvical spinal cord. The action of cirazoline was blocked by s.c. prazo sin but not by 5-HT1A antagonists such as (-)-alprenolol, indicating t hat the alpha(1)-adrenoceptors mediating STFs lie downstream of 5-HT1A receptors. Further, cirazoline-induced STFs were not affected by alph a(2)-agonists and -antagonists, suggesting that the alpha(2)-adrenocep tors inhibiting STFs are localized presynaptically to these alpha(1)-a drenoceptors. In rats in which lumbar spinal cord pools of noradrenali ne were depleted by 6-hydroxydopamine, STFs evoked by cirazoline were potentiated, indicating supersensitivity of postsynaptic alpha(1)-adre noceptors. In contrast, 8-OH-DPAT-induced STFs were diminished. In con clusion, spinal populations of alpha(1) (alpha(1A))- and alpha(2) (alp ha(2D))- adrenoceptors respectively mediate and inhibit the induction of STFs by 5-HT1A receptor agonists, the actions of which depend on a functionally intact, descending, noradrenergic projection to lumbar sp inal cord.