Effects of naloxone on amphetamine induced striatal dopamine release in vivo: a microdialysis study

The opiate antagonist naloxone (NX) alters amphetamine (AMPH) induced behaviors including locomotor activity, rearing and stereotypy. However, the exact nature of the NX induced alteration of AMPH induced behaviors is controversial, with some studies using high (5-40 mg/kg) doses of NX reporting an inhibition, and others using low (< or = 1-2 mg/kg) doses observing a potentiation. As these behaviors are mediated by AMPH induced dopamine (DA) release, the effect of NX on the latter was examined by microdialysis in an effort to resolve the controversy. Saline and NX pretreated groups subsequently administered AMPH were compared in vivo across nine separate 10 min intervals as well as by grouped intervals. NX alone (0.8 mg/kg) and saline exerted statistically equivalent effects on striatal DA release with the exception of the fifth interval, where a small but significant increase was seen after NX. On the other hand, the same dose of NX significantly enhanced AMPH induced striatal DA release relative to saline pretreated animals during each of four separate intervals, from 30 to 70 minutes following AMPH (1.5 mg/kg), and across all nine intervals combined. NX pretreatment (0.8 mg/kg) followed by a higher dose of AMPH (3.0 mg/kg) produced a significantly greater cumulative effect on DA release than saline pretreatment over the last six combined intervals (30-90 min) and over two grouped intervals (30-50 min and 40-60 min inclusive). However, a comparison of single rather than paired or grouped intervals revealed no significant differences. Previous studies have also examined the effect of NX on AMPH induced striatal DA release using in vivo microdialysis. However, the doses used were invariably high (5 mg/kg) and the results on striatal DA release always inhibitory. The present results suggest that NX potentiates AMPH induced striatal DA release when lower doses of NX are used. These results combined with those of previous studies also suggest that NX exerts a biphasic effect on AMPH induced DA release, with lower doses potentiating release and higher doses inhibiting release. This is close agreement with behavioral observations and may be due to the effect of low versus high doses of NX on intraterminal calcium influx.