Muscarinic and alpha(1)-adrenergic mechanisms contribute to the spinal mediation of stimulation-induced antinociception from the pedunculopontine tegmental nucleus in the rat.
The effects of intraperitoneal (i.p.) or intrathecal (i.t.) injection of antagonists of acetylcholine, noradrenaline, serotonin, dopamine, opioids and GABA on stimulation-produced antinociception (SPA) from the pedunculopontine tegmental nucleus (PPTg) of rats were studied using the tail-flick test. The electrical stimulation of the PPTg produced a strong and long-lasting increase in tail-flick latency. The intensity and duration of the effect were significantly reduced in rats pretreated with i.p. or i.t. atropine (a non-selective muscarinic cholinergic antagonist), or i.t. phenoxybenzamine or WB 4101 (non-selective and selective alpha(1)-adrenergic antagonists, respectively). Intraperitoneal phenoxybenzamine, i.p. or i.t. methysergide or naloxone (non-selective serotonin and opioid antagonists, respectively), or i.t. idazoxan (a selective alpha(2)-adrenergic antagonist) only reduced the duration of the effect. The duration of SPA from the PPTg was increased by i.t. phaclofen (a GABA(B) antagonist). The effect from the nucleus was not altered following i.t. bicuculline (a GABA(A) antagonist), or i.p. or i.t. mecamylamine, propranolol or haloperidol (non-selective nicotinic cholinergic, beta-adrenergic and dopaminergic antagonists, respectively). Thus, SPA from the PPTg involves the spinal activation of muscarinic and alpha(1)-adrenergic but not nicotinic cholinergic, beta-adrenergic and dopaminergic mechanisms. Serotonergic, endogenous opioid and alpha(2)-adrenergic mechanisms are involved in the duration but not in the intensity of the effect.
Dias
Quintino M
QM
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto-USP, Ribeirão Preto, SP, Brazil.
Crespilho
Simone F
SF
Silveira
João Walter S
JW
Prado
Wiliam A
WA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D007278:Injections, Spinal; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D018727:Muscarinic Antagonists; D018340:Receptors, Adrenergic, alpha-1; D011976:Receptors, Muscarinic