The behavioural response to intrathecal serotonin is changed by acute but not by repeated treatment with zimelidine or metergoline.
The behavioural response to intrathecal serotonin (5-HT) was examined in mice after acute and after withdrawal of repeated treatment with the 5-HT uptake inhibitor zimelidine or the 5-HT receptor antagonist metergoline. Intrathecal 5-HT elicits a response consisting of biting or licking of the lower part of abdomen and reciprocal hindlimb scratching, indicative of nociceptive stimulation. Acute injection of zimelidine (20 mg/kg) significantly increased the response to intrathecal 5-HT (0.25-1 micrograms) whereas a single dose of metergoline (5 mg/kg) completely blocked the response to intrathecal 5-HT (2 micrograms). The behavioural response to intrathecal 5-HT (0.25-2 micrograms) was not significantly changed 48 hr after withdrawal of repeated treatment with zimelidine (2 x 10 mg/kg/day for 14 days) or metergoline (2 x 2.5 mg/kg/day for 14 days). In the present experiments acute zimelidine appeared to increase nociceptive responsiveness, whereas metergoline had the opposite effect. This study does not provide evidence that long-term treatment with zimelidine or metergoline leads to adaptive changes in the response to spinal cord 5-HT receptor stimulation.
Eide
P K
PK
Department of Physiology, University of Bergen, Norway.
Joly
N M
NM
Lund
A
A
D000818:Animals; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D008711:Metergoline / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D015031:Zimeldine / Q000008:administration & dosage / Q000494:pharmacology*
D011985:Receptors, Serotonin; D008711:Metergoline; D012701:Serotonin; D015031:Zimeldine