Cold water swim stress- and delta-2 opioid-induced analgesia are modulated by spinal gamma-aminobutyric acidA receptors.
Cold water swim stress for 3 min at 5 degrees C produces antinociception in the tail-flick test in mice by activation of delta opioid receptors in the brain. Also, the inhibition of the tail-flick reflex produced by i.c.v. administration of delta opioid receptor agonists is known to be mediated by spinal gamma-aminobutyric acid (GABA) receptors. The purpose of this investigation was to determine if the cold water swim stress-induced antinociceptive response is mediated by GABA receptors in the spinal cord. First, i.c.v. administration of the delta-2 receptor antagonist, naltriben, but not the delta-1 receptor antagonist, 7-benzylidenenaltrexone, antagonized the cold water swim stress-induced antinociception in ICR mice and confirmed the role of delta-2 receptors in this response. Next, the involvement of spinal GABAA receptors was shown through intrathecal administration of GABAA receptor antagonists, picrotoxin and bicuculline, which inhibited the cold water swim stress-induced antinociceptive response. Thus, the antinociception produced through activation of the delta-2 receptor in the brain by cold water swim stress involved a descending pathway mediated by spinal GABAA receptors. This descending pathway appeared to be the same as that activated by i.c.v. administration of delta-2 opioid agonists in the brain.
Killian
P
P
Research Service, Veteran's Affairs Medical Center, Milwaukee, Wisconsin, USA.
Holmes
B B
BB
Takemori
A E
AE
Portoghese
P S
PS
Fujimoto
J M
JM
D000698:Analgesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*; D013550:Swimming
D009271:Naltrexone; D010852:Picrotoxin; D011963:Receptors, GABA-A; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran