EFFECTS OF PHENTERMINE ON STRIATAL DOPAMINE AND SEROTONIN RELEASE IN CONSCIOUS RATS - IN-VIVO MICRODIALYSIS STUDY

OBJECTIVE: To measure the effects of phentermine, an appetite supressa nt, on the release of brain dopamine (DA) and serotonin (5-HT) into st riatal dialysates of freely moving rats. DESIGN: Microdialysis and hig h performance liquid chromatography. SUBJECTS: Unanesthetized rats. ME ASUREMENTS: Samples collected every 20 min were assayed for both neuro transmitters in a single run, using high performance liquid chromatogr aphy with electrochemical detection. RESULTS: Baseline levels of DA an d 5-HT in dialysates were 56 +/- 16 and 3 +/- 0.6 fmol/20 mu l, respec tively. Administration of phentermine (2 or 5 mg/kg) increased dialysa te DA concentrations to 147 +/- 17% (P < 0.01) and 320 +/- 89% (P (0.0 1) of baseline, respectively, without significantly affecting 5-HT con centrations. Pretreatment with tetrodotoxin (TTX, 60 min, 1 mu M), whi ch abolished the basal release of DA and 5-HT into striatal dialysates , diminished the increase in DA concentrations induced by phentermine, but did not completely block it. Phentermine (2 or 5 mg/kg, i.p.) sti ll stimulated DA release to 27 +/- 13% and 85 +/- 15% of baseline, res pectively, in the presence of TTX. CONCLUSION: Phentermine increases b rain DA but not 5-HT release in freely moving rats, and TTX reduces, b ut does not fully block this effect. This pattern is similar to that k nown to be produced by d-amphetamine.