Excitatory Modulation of Hippocampus on Amphetamine-induced Hyperactivity in Rats

Institution

Morehead State University

Abstract

Psychostimulants, such as amphetamine and cocaine, produce hyperactivity in mammalian species. Hyperactive behavior is thought partly due to excessive dopamine in the nucleus accumbens (NAc). Recent evidence indicates that stimulation of the hippocampus (HIP) also produces hyperactivity, possibly via modulation of dopamine in NAc. The present study investigated hippocampal modulation of hyperactivity induced by amphetamine in rats. Hippocampal stimulation was done via NMDA infusions into the ventral hippocampus. Hippocampal inhibition was done via lidocaine infusions. Amphetamine was infused into NAc to enhance dopamine transmission in NAc. We tested the hypothesis that excitation or inhibition of HIP would differentially affect dopamine-induced hyperactivity: stimulation of HIP would augment hyperactivity, whereas inhibition of HIP would decrease hyperactivity. Wistar rats were anesthetized, were surgically implanted with bilateral cannulae for subsequent microinfusions, and were allowed 7-10 days for recovery. We found that amphetamine (10mg/ml, 0.5 microliter/site) infusions into NAc produced hyperactivity, measured by distance traveled. Hippocampal stimulation augmented hyperactivity induced by amphetamine infusions in NAc. Hippocampal inhibition blocked amphetamine-induced hyperactivity. The present findings support our hypothesis and provide evidence for a critical involvement of hippocampus in expression of hyperactivity possibly via modulation of dopamine and another neurotransmitter, such as glutamate in NAc. Future research on the precise role of hippocampus in hyperactivity will expand our understanding of hyperactivity disorders associated with dysfunction of the mesolimbic system.

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Excitatory Modulation of Hippocampus on Amphetamine-induced Hyperactivity in Rats

Psychostimulants, such as amphetamine and cocaine, produce hyperactivity in mammalian species. Hyperactive behavior is thought partly due to excessive dopamine in the nucleus accumbens (NAc). Recent evidence indicates that stimulation of the hippocampus (HIP) also produces hyperactivity, possibly via modulation of dopamine in NAc. The present study investigated hippocampal modulation of hyperactivity induced by amphetamine in rats. Hippocampal stimulation was done via NMDA infusions into the ventral hippocampus. Hippocampal inhibition was done via lidocaine infusions. Amphetamine was infused into NAc to enhance dopamine transmission in NAc. We tested the hypothesis that excitation or inhibition of HIP would differentially affect dopamine-induced hyperactivity: stimulation of HIP would augment hyperactivity, whereas inhibition of HIP would decrease hyperactivity. Wistar rats were anesthetized, were surgically implanted with bilateral cannulae for subsequent microinfusions, and were allowed 7-10 days for recovery. We found that amphetamine (10mg/ml, 0.5 microliter/site) infusions into NAc produced hyperactivity, measured by distance traveled. Hippocampal stimulation augmented hyperactivity induced by amphetamine infusions in NAc. Hippocampal inhibition blocked amphetamine-induced hyperactivity. The present findings support our hypothesis and provide evidence for a critical involvement of hippocampus in expression of hyperactivity possibly via modulation of dopamine and another neurotransmitter, such as glutamate in NAc. Future research on the precise role of hippocampus in hyperactivity will expand our understanding of hyperactivity disorders associated with dysfunction of the mesolimbic system.