Effects of nucleus accumbens amphetamine on lateral hypothalamic brain stimulation reward

The effects of amphetamine were examined in a brain stimulation reward paradigm in which response rate was measured across a range of stimulation frequencies. Both low (0.0625 and 0.125 mg/kg) and high (1.0, 2.0 and 4.0 mg/kg) doses of systemic amphetamine decreased the stimulation frequency needed to sustain low rates of responding; high doses decreased the maximal response rates that were sustained by the highest stimulation frequencies. Ipsilateral microinjections (2.5, 5.0 and 10.0 micrograms/0.5 microliter) of D-amphetamine sulfate into the nucleus accumbens also caused shifts to the left of the rate-frequency function; no central dose caused a change in the asymptotic response rate associated with high stimulation frequencies. Contralateral injections of D-amphetamine (10.0 micrograms) also shifted the rate-frequency functions to the left, but were much less potent. Ipsilateral injections of D-amphetamine into the caudate were also less potent, suggesting nucleus accumbens rather than more dorsal tissue as the site of this behavioral action. Also less potent were the effects of L-amphetamine, ruling out non-specific effects of pH, osmolarity and the like and also ruling out noradrenergic actions as explanations of the behavioral effects of the injections. These data suggest that nucleus accumbens is a site of amphetamine's reward-enhancing and threshold-lowering effects on brain stimulation reward.