Sequential mediation of norepinephrine-and dopamine-induced antinociception at the spinal level: involvement of different local neuroactive substances.
The effects of intrathecally (i.t.) administered opioid antagonist naloxone (Nal), adenosine antagonist aminophylline (Aph), and gamma-aminobutyric acid (GABAA)-receptor antagonist picrotoxin (PTX) or Bicuculline (BIC) 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 GABAA-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 increases in tail-flick latencies (antinociception); (2) both Nal (240 nmol) and Aph (120 nmol) blocked the antinociception produced by NE (1.0 nmol); (3) both Nal (240 nmol) and Aph (120 nmol) blocked the antinociception 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 antinociception 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 MUS (1.0 nmol). These results suggest that: (a) endogenous opiate and adenosine may be involved in the mediation of NE-induced, but not DA-induced, antinociception; (b) NE, opioid and adenosine may act in a sequential order in NE-induced antinociception at the spinal level; (c) endogenous GABA may be involved in the mediation of DA-induced antinociception through the GABAA-receptors, but is not involved in NE-induced antinociception at the spinal level.
Yang
S W
SW
Department of Neurobiology, Shanxi Medical College, Taiyuan, People's Republic of China.
Zhang
C
C
Zhang
Z H
ZH
Qiao
J T
JT
Dafny
N
N
D000818:Animals; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology*; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology*
D018755:GABA Agonists; D018756:GABA Antagonists; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D010726:Phosphodiesterase Inhibitors; D013566:Sympathomimetics; D004298:Dopamine; D009638:Norepinephrine