Cyclosporine affects central nervous system opioid activity via direct and indirect means

It is demonstrated that cyclosporine (CsA), a novel fungal-derived immunosuppressive agent, attenuates naloxone-precipitated morphine withdrawal in an unusual dose-dependent manner following direct intracerebroventricular (icv) administration. However, comparison and contrast of this effect of CsA following icv versus ip administration demonstrates that although CsA does alter the severity of withdrawal by a direct effect within the CNS, the agent is most effective when given systemically. It is also demonstrated that CsA alters the electrophysiologic properties of discrete brain nuclei both when given alone and when given concomitant with morphine and naloxone.