Analgesia and motor activity following administration of THIP into the periaqueductal gray and lateral ventricle of rats

Abstract

Retz, K.C., and L.M. Holaday: Analgesia and motor activity following administration of THlP into the periaqueductal gray and lateral ventricle of rats. Drug Dev. Res. 9:133-142, 1986. lntracerebral microinjections of THlP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a GABAergic agonist that produces analgesia when administered systemically, were made to investigate the central sites of action of this agent. Comparisons were also made with intracerebral microinjections of morphine and with systemic administration of each agent. Injections into the ventral lateral periaqueductal gray (PAG) produced analgesia on the 55OC hot-plate test following a 2.0 pg dose, but were without effect at the other doses examined (0.5-20.0 pg). In the tail-flick test, hyperalgesia was seen following the 5.0-and 20.0-pg doses. Motor activity was increased following the 1.0-, 2.0-, and 10.0-pg doses and was accompanied by ipsilateral turning. Injections into the lateral cerebral ventricle (ICV) were without effect at doses of less than 50 pg. No significant effects were observed in the hot-plate test following 50 pg; 100 pg produced severe ataxia, precluding testing. Following 50 pg, hyperalgesia was seen in the tail-flick test. THlP at both doses decreased motor activity. The present findings further demonstrate some novel aspects of the pharmacology of THlP and suggest that much of the drug's analgesic activity is produced by interaction with GABAergic receptors outside the PAG and structures easily accessed by ICV administration.