Site-specific modulation of morphine and swim-induced antinociception following thyrotropin-releasing hormone in the rat periaqueductal gray.

Central administration of thyrotropin-releasing hormone (TRH) produces a short-lived antinociceptive response in rats, and also modulates opioid and non-opioid forms of antinociception. Given the presence of TRH cells, fibers and receptors in the periaqueductal gray (PAG), the present study examined the effects of TRH administered into the PAG upon antinociception following either continuous cold-water swims (CCWS, 2 degrees C for 3.5 min) or morphine (0.1-2.5 micrograms) administered into the PAG on the tail-flick and jump tests, and measured changes in core body temperatures as well. Histological examination revealed two groups in which anterior PAG placements were found rostral to the dorsal raphe nucleus, and posterior PAG placements which were at the level of this nucleus. TRH produced brief (5-15 min) but significant increases in latencies and thresholds without altering body temperature in both anterior and posterior PAG placements. Whereas TRH in anterior PAG placements dose dependently (0.1-10 micrograms) decreased CCWS antinociception on both tests, TRH in posterior PAG placements significantly increased CCWS antinociception on the jump test. TRH in both placements reduced the magnitude of CCWS hypothermia. TRH significantly potentiated the magnitude and duration of both morphine antinociception and hyperthermia in both anterior and posterior PAG placements, and shifted mesencephalic morphine's antinociceptive dose-response curve significantly to the left. These data are discussed in terms of the role of the PAG in opioid and non-opioid forms of stress-induced antinociception as well as morphine antinociception, and in terms of the roles of TRH and anterior PAG placements as potential candidates for a collateral inhibition model of antinociceptive responses.