Amphetamine-induced hyperlocomotion in rats: Hippocampal modulation of the nucleus accumbens

Using lesions and infusions, the present study investigated the way in which and the extent to which the ventral hippocampus (vHIP) modulates amphetamine-induced hyperactivity in rats. Rats were lesioned (excitotoxic or sham) in the vHIP or were implanted with cannulae for subsequent infusions. A high dose (12.5 microg/microl) of N-methyl-D-aspartate (NMDA) was used to make excitotoxic lesions and a low dose (0.5 microg/microl) of NMDA to cause activation of the hippocampus. Lidocaine was used to inactivate the hippocampus. Lidocaine or a low dose of NMDA was infused into the vHIP in combination with either systemic injection or intra-accumbens infusions of amphetamine. The effects of these treatments on locomotor activity were measured by distance traveled in 10-min intervals for 40-60 min. Lesions and deactivation of the hippocampus attenuated amphetamine-induced hyperlocomotion, compared to the controls. Stimulation of the hippocampus augmented amphetamine-induced hyperlocomotion. The present findings provide evidence that the hippocampus exerts excitatory modulation on the expression of behavioral excitation produced by amphetamine, likely via the nucleus accumbens.