Attenuation of morphine-induced analgesia by p-chlorophenylalanine and p-chloroamphetamine: test-dependent effects and evidence for brainstem 5-hydroxytryptamine involvement.
A number of studies on the role of 5-HT in morphine analgesia and regulation of nociception are reviewed. Highly divergent conclusions are found in the literature with regard to the importance of serotonergic structures. Several methodological differences, particularly with regard to lesion and depletion techniques and testing procedures, may account for the controversies in the literature. The experimental findings presented demonstrate attenuation of morphine-induced analgesia in the hot-plate and tail-flick tests, and increased responsiveness to noxious electrical shock following depletion of 5-HT in ascending and descending 5-HT pathways by PCPA (200 + 100 + 100 mg/kg on 3 consecutive days prior to testing) as well as following destruction of cerebral 5-HT terminals by PCA (2 X 10 mg/kg, 7 and 8 days before testing). This was also the case when the neurotoxic effect of PCA was largely restricted to the brainstem by pretreatment with the 5-HT reuptake inhibitor zimelidine (20 mg/kg prior to each PCA injection). Attenuation of morphine analgesia was not found in the flinch-jump test or in the hot-plate test when conducted immediately after flinch-jump testing. It is concluded that brainstem 5-HT connections may contribute to the analgetic effect of morphine, but only under certain test conditions.
D000662:Amphetamines / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D010134:Fenclonine / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D000662:Amphetamines; D012701:Serotonin; D010133:p-Chloroamphetamine; D009020:Morphine; D010134:Fenclonine