COLD-WATER SWIM STRESS-INDUCED AND DELTA-2-OPIOID-INDUCED ANALGESIA ARE MODULATED BY SPINAL GAMMA-AMINOBUTYRIC-ACID(A) RECEPTORS

Cold water swim stress for 3 min at 5 degrees C produces antinocicepti on in the tail-flick test in mice by activation of delta opioid recept ors in the brain. Also, the inhibition of the tail-flick reflex produc ed by i.c.v. administration of delta opioid receptor agonists is known to be mediated by spinal gamma-aminobutyric acid (GABA) receptors. Th e purpose of this investigation was to determine if the cold-water swi m stress-induced antinociceptive response is mediated by GABA receptor s in the spinal cord. First, i.c.v. administration of the delta-2 rece ptor 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-e receptor s in this response. Next, the involvement of spinal GABA(A) receptors was shown through intrathecal administration of GABA(A) receptor antag onists, picrotoxin and bicuculline, which inhibited the cold water swi m stress-induced antinociceptive response. Thus, the antinociception p roduced through activation of the delta-2 receptor in the brain by col d water swim stress involved a descending pathway mediated by spinal G ABA(A) receptors. This descending pathway appeared to be the same as t hat activated by i.c.v. administration of delta-2 opioid agonists in t he brain.