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Role of spinal 5‐HT 1A receptors in morphine analgesia and tolerance in rats
Author(s) -
Bardin Laurent,
Colpaert Francis C.
Publication year - 2004
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2003.09.002
Subject(s) - morphine , pharmacology , chemistry , analgesic , nociception , agonist , 5 ht receptor , opioid , μ opioid receptor , receptor , serotonin , anesthesia , medicine , biochemistry
We here studied the involvement of spinally located 5‐HT 1A and opioid receptors, in the paradoxical effects that their activation can produce on nociception. Intrathecal (i.t.) injection of the 5‐HT 1A receptor agonist 8‐hydroxy‐2‐{di‐ n ‐propylamino} tetralin (8‐OH‐DPAT) (1–10 μg) induced analgesic effects in the formalin model of tonic pain whereas in the paw pressure test, it decreased the vocalization threshold. In this latter test, i.t. 8‐OH‐DPAT also markedly reduced the analgesic effect of systemic morphine (5–10 mg/kg, s.c.). At 10 μg, 8‐OH‐DPAT totally abolished the effect of 5 mg/kg of morphine; this inhibitory effect was antagonized by pre‐treatment with 0.63 mg/kg of the 5‐HT 1A antagonist WAY‐100635 ( N {2‐{4‐(2‐methoxyphenyl)‐1‐piperazinyl}‐ethyl}‐ N ‐(2‐pyridinyl)‐cyclohexanecarboxamide‐trihydrochloride). In contrast, the i.t. injection of WAY‐100635 (1–10 μg) dose‐dependently potentiated the antinociceptive activity of a dose of morphine (2.5 mg/kg, s.c.). Furthermore, WAY‐100635 (10 μg, i.t.) potentiated morphine analgesia in morphine‐tolerant rats. These findings demonstrate that 5‐HT 1A receptor agonists can act in the spinal cord to produce both hyper‐ and hypo‐algesic effects and play a major role in the opioid analgesia and tolerance.