SEQUENTIAL MEDIATION OF NOREPINEPHRINE-INDUCED AND DOPAMINE-INDUCED ANTINOCICEPTION AT THE SPINAL LEVEL - INVOLVEMENT OF DIFFERENT LOCAL NEUROACTIVE SUBSTANCES

The effects of intrathecally (i.t.) administered opioid antagonist nal oxone (Nal), adenosine antagonist aminophylline (Aph), and gamma-amino butyric acid (GABA(A))-receptor antagonist picrotoxin (PTX) or Bicucul line (BIG) on the antinociception produced by i.t. norepinephrine (NE) , dopamine (DA), morphine (Mor), 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine agonist) or muscimol (MUS, a selective GABA(A)-receptor agonist) were studied and compared using the tail-flick test in rats. The results showed that: (1) both i.t. NE (0.3, 0.5 and 1.0 nmol) and DA (5.5, 8.3 and 16.5 nmol) produced significant and dose-dependent in creases in tail-flick latencies (antinociception); (2) both Nal (240 n mol) and Aph (120 nmol) blocked the antinociception produced by NE (1. 0 nmol); (3) both Nal (240 nmol) and Aph (120 nmol) blocked the antino ciception produced by Mor (0.5 nmol), but only Aph (120 nmol) blocked the antinociception produced by NECA (0.5 nmol), while Nal (240 nmol) did not; (4) neither Nal (240 nmol) nor Aph (120 nmol) altered the ant inociception produced by DA (16.5 nmol); (5) both i.t. PTX (1.5 nmol) and BIC (0.5 nmol) completely blocked the antinociception produced by DA (16.5 nmol), but showed no effects on that produced by NE (1.0 nmol ); and (6) both PTX and BIC blocked the antinociception produced by MU S (1.0 nmol). These results suggest that: (a) endogenous opiate and ad enosine may be involved in the mediation of NE-induced, but not DA-ind uced, antinociception; (b) NE, opioid and adenosine may act in a seque ntial order in NE-induced antinociception at the spinal level; (c) end ogenous GABA may be involved in the mediation of DA-induced antinocice ption through the GABA(A)-receptors, but is not involved in NE-induced antinociception at the spinal level.