Neuroendocrine effects of d-fenfluramine and bromocriptine following repeated smoked cocaine in humans

To study the consequences of repeated smoked cocaine use on central seroton ergic and dopaminergic function, the effects of d-fenfluramine (d-FEN) and bromocriptine on plasma hormones were determined at three time-points follo wing repeated cocaine self-administration under carefully controlled condit ions. In a 20-day inpatient study, male cocaine abusers (d-FEN: n = 10; bro mocriptine: n = 8) self-administered smoked cocaine (12-50 mg) for 3 days f ollowed by 2 weeks of abstinence. The acute effects of d-FEN (0 or 30 mg po ) or bromocriptine (0 or 1.25 mg po) on plasma neuroendocrine levels were d etermined 1-2, 7-8, and 13-14 days after the last cocaine dose. Blood was d rawn before and then every 30-60 min for 4 h after capsule administration. The effects of d-FEN and bromocriptine were also determined in healthy, out patient controls, d-FEN was removed from medical use in the US midway throu gh the study due to complications associated with chronic administration, s o all of the control participants were tested in Italy. Cocaine users had a blunted prolactin and cortisol response to d-FEN that lasted for at least 2 weeks of cocaine abstinence, but had a normal response to bromocriptine, which suppressed prolactin by 50% of baseline. The long-lasting and selecti ve disruptions in serotonin pathways following chronic cocaine use may prov ide a neurochemical basis for changes in mood commonly reported during coca ine withdrawal. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.