Involvement of supraspinal and spinal CCK receptors in the modulation of antinociception induced by cold water swimming stress in the mouse.

We have previously reported that supraspinally and spinally located CCK receptors are involved in antagonizing supraspinally administered opioid-induced antinociception. Cold water swimming stress (CWSS) produces antinociception and opioid receptors are involved in CWSS-induced antinociception. The present study was designed to determine if supraspinal and spinal CCK receptors were involved in modulating the CWSS- induced antinociception. Antinociception was assessed by the tail-flick test. CWSS caused a profound inhibition of the tail-flick response. Various doses of CCK injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.) alone did not show any antinociceptive effect. The i.c.v. or i.t. pretreatment with CCK (0.05-0.5 ng) dose dependently attenuated the CWSS- induced inhibition of the tail-flick response. In addition, i.c.v. pretreatment with lorglumide (0.1-10 pg) but not PD135,158 (1-100 pg) dose dependently reversed CCK's inhibition of the tail-flick response induced by CWSS. However, both lorglumide and PD135,158 injected i.t. reversed the antagonism of CCK against the inhibition of the tail-flick response induced by CWSS in a dose-dependent manner. Our results suggest that, at the supraspinal level, CCK(A) but not CCK(B) receptors may be involved in antagonizing the CWSS-induced antinociception. In the spinal cord both CCK(A) and CCK(B) receptors appear to be involved in antagonizing the CWSS-induced antinociception.