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.