THE BEHAVIORAL-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-mu-g) whereas a single dose of metergoline (5 mg/kg) completely blocked the response to intrathecal 5-HT (2-mu-g). The behavioural response to intrathecal 5-HT (0.25-2-mu-g) 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.