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

To study the consequences of repeated smoked cocaine use on central serotonergic and dopaminergic function, the effects of d-fenfluramine (d-FEN) and bromocriptine on plasma hormones were determined at three time-points following repeated cocaine self-administration under carefully controlled conditions. In a 20-day inpatient study, male cocaine abusers (d-FEN: n=10; bromocriptine: n=8) self-administered smoked cocaine (12-50 mg) for 3 days followed 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 determined 1-2, 7-8, and 13-14 days after the last cocaine dose. Blood was drawn 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, outpatient controls; d-FEN was removed from medical use in the US midway through the study due to complications associated with chronic administration, so 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 selective disruptions in serotonin pathways following chronic cocaine use may provide a neurochemical basis for changes in mood commonly reported during cocaine withdrawal.