The relative contribution of ascending and descending serotonergic pathways in p-chloroamphetamine-induced antinociception.
Systemic administration in rats of p-chloroamphetamine (PCA; 2 x 10 mg/kg) reduced the in vitro uptake of 14C-5-hydroxytryptamine (14C-5-HT) in cortical synaptosomes by 76% and in spinal cord synaptosomes by 35%. Intrathecal injection of 5,6-dihydroxytryptamine (20 micrograms/rat) selectively lesioned the descending serotonergic pathways (83% reduction in uptake of 14C-5-HT in spinal synaptosomes, no significant change in uptake in cortical synaptosomes). Administration of PCA or 5,6-DHT did not significantly alter the uptake of 3H-noradrenalin into cortical or spinal synaptosomes. The response thresholds of the rats in the increasing temperature hot plate test (1 to 7 days after administration) were unaffected by either type of lesion. Interference with the antinociceptive effect of PCA (2.5 mg/kg) was evaluated 7 days after administration of the neurotoxins. PCA pretreatment strongly reduced the peak of the PCA-induced antinociception while 5,6-DHT reduced its duration. Thus, both ascending and descending serotonergic pathways contribute to PCA-induced antinociception.
Bjørkum
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Department of Physiology, University of Bergen, Norway.
Berge
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D015115:5,6-Dihydroxytryptamine / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D008297:Male; D009434:Neural Pathways / Q000187:drug effects*; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects; D013997:Time Factors; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D000662:Amphetamines; D012701:Serotonin; D010133:p-Chloroamphetamine; D015115:5,6-Dihydroxytryptamine