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Analgesia and motor activity following administration of THIP into the periaqueductal gray and lateral ventricle of rats
Author(s) -
Retz Konrad C.,
Holaday Lisa M.
Publication year - 1986
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430090206
Subject(s) - microinjections , periaqueductal gray , agonist , pharmacology , gabaergic , chemistry , muscimol , morphine , systemic administration , medicine , anesthesia , endocrinology , microinjection , central nervous system , midbrain , receptor , in vivo , biology , microbiology and biotechnology
Intracerebral microinjections of THIP (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 periqueductal gray (PAG) produced analgesia on the 55 ° C hot‐plate test following a 2.0 μg dose, but were without effect at the other doses examined (0.5–20.0 μg). In the tail‐flick test, hyperalgesia was seen following the 5.0‐ and 20.0‐μg doses. Motor activity was increased following the 1.0‐, 2.0‐, and 10.0‐μg doses and was accompanied by ipsilateral turning. Injections into the lateral cerebral ventricle (ICV) were without effect at doses of less than 50 μg. No significant effects were observed in the hot‐plate test following 50 μg produced severe ataxia, precluding testing. Following 50 μg, hyperalgesia was seen in the tail‐flick test. THIP at both doses decreased motor activity. The present findings further demonstrate some novel aspects of the pharmacology of THIP 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.