[ effect of intrathecal administration of cocaine and serotonergic antagonist [cyproheptadine] on nociception in rat]

ABSTRACT

Cocaine by effect on central nervous system inhibits reuptake of monoamines [serotonin, norepinephrine and dopamine] to presynaptic terminal and increases their concentration. Monoamines such as serotonin cause analgesia at the spinal level. This study investigates the effects of systemic and spinal administration of cocaine on pain sensation and the relation between these effects and serotonin. Male Wistar rats [200-250g] were set in groups saline [i.p], saline/DMSO [i.p], cocaine 25mg/kg [i.p], saline [i.t], saline/DMSO [i.t], cocaine 100micro g/10 micro l [i.t], cyproheptadine 33 micro g/10 micro l [i.t.] and cyproheptadine 33 micro g/10 micro l/cocaine 100 micro g/10 micro l [i.t]. Tail flick latency was measured before and after administration. Intraplantar formalin was used for induction of chemical pain. The data was analyzed by T-Test and ANOVA. Pain in both phases of formalin test was reduced in both cocaine 25mg/kg [i.p] [P<0.01] and cocaine 100 micro g/10 micro l [i.t.] [P<0.01]. However, in cyproheptadine 33 micro g/10 micro l [i.t], was increased in the first phase [P<0.01]. In cyproheptadine 33 micro g/10 micro l/cocaine 100 micro g/10 micro l [i.t.], the part of pain reduction induced by cocaine was reversed, in both phases [P<0.01]. In tail flick test the results of cyproheptadine 33 micro g/10 micro l [i.t.] showed reduced tail flick latency [P<0.001]. Inhibition of serotonin reuptake at the spinal level plays role in analgesic effects of cocaine probably, because release of serotonin from the spinal serotonergic terminals causes inhibition of pain neurons and reduction of pain. In addition, inhibition of spinal serotonin receptors by cyproheptadine reduced part of analgesic effects of cocaine probably