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 supressant, on the release of brain dopamine (DA) and serotonin (5-HT) into striatal dialysates of freely moving rats. DESIGN: Microdialysis and high performance liquid chromatography. SUBJECTS: Unanesthetized rats. MEASUREMENTS: Samples collected every 20 min were assayed for both neurotransmitters in a single run, using high performance liquid chromatography with electrochemical detection. RESULTS: Baseline levels of DA and 5-HT in dialysates were 56 +/- 16 and 3 +/- 0.6 fmol/20 mu l, respectively. Administration of phentermine (2 or 5 mg/kg) increased dialysate DA concentrations to 147 +/- 17% (P < 0.01) and 320 +/- 89% (P (0.01) of baseline, respectively, without significantly affecting 5-HT concentrations. Pretreatment with tetrodotoxin (TTX, 60 min, 1 mu M), which 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.) still stimulated DA release to 27 +/- 13% and 85 +/- 15% of baseline, respectively, in the presence of TTX. CONCLUSION: Phentermine increases brain DA but not 5-HT release in freely moving rats, and TTX reduces, but does not fully block this effect. This pattern is similar to that known to be produced by d-amphetamine.