The Effect of Cocaine and Serotonergic Antagonist (Cyproheptadine) on Inflammatory Paw Edema in Rat

Background: Cocaine is a central nervous system stimulant and is an inhibitor of monoamine (serotonin, norepinephrine and dopamine) reuptake; so increases their concentration in central nervous system. Monoamines such as serotonin and nor epinephrine have a role in anti-inflammatory effects and in modulating of immune system. The aim of this study was to investigate the effect of systemic and spinal administration of cocaine (none selective inhibitor of monoamine reuptake) on inflammatory paw edema and the role of serotonin neurotransmitter in these effects at the spinal level. Methods: 56 Male Wistar rats (200-250 g) were set in 8 groups: Intraperitoneal Saline, Intraperitoneal Saline/Dimethyl sulfoxide (DMSO), Intraperitoneal Cocaine 25 mg/kg, Intrathecal Saline, Intrathecal Saline/DMSO, Intrathecal Cocaine 100 µg/10 µl, Intrathecal Cyproheptadine 33 µg/10 µl and Intrathecal Cyproheptadine 33 µg/10 µl/Cocaine 100 µg/10 µl. Inflammation was induced by subplantar injection of formalin. Findings: Anti-inflammatory effects of cocaine was significant in intraperitoneal cocaine 25 mg/kg (P < 0.001) and intrathecal cocaine 100 µg/10 µl (P < 0.001) groups. In intrathecal cyproheptadine 33 µg/10 µl group, there was no influence on inflammation. In intrathecal cyproheptadine 33 µg/10 µl/cocaine 100 µg/10 µl, cyproheptadine decreased a part of anti-inflammatory effect of cocaine (P < 0.001). Conclusion: Serotonergic terminals coming from higher center to the spinal cord interacts with spinal neurons such as primary afferent C fibers. Probably, the inhibition of primary afferent fibers by serotonin inhibits release of inflammatory agent from these fibers and causes anti-inflammatory effects. It is likely that inhibition of serotonin receptor at the spinal level by intrathecal administration of cyproheptadine has reduced anti-inflammatory effects of cocaine.