Chronic methylphenidate modulates locomotor activity and sensory evoked responses in the VTA and NAc of freely behaving rats

Repeated exposure to psychostimulants leads to behavioral sensitization. The mode of action of brain circuitry responsible for behavioral sensitization is not well understood. There is some evidence that psychostimulants, such as amphetamine and cocaine, activate the ventral tegmental area (VTA) and nucleus accumbens (NAc). However, little is known about the effect of methylphenidate (MPD) on the electrophysiological properties of VTA and NAc neurons. The study was designed to investigate the chronic effects of MPD administration on sensory evoked field potentials of VTA and NAc in freely behaving rats previously implanted with permanent electrodes. On experimental day 1, locomotor behavior was recorded for 2 h post-saline injection followed by sensory evoked field potential recordings after saline and three different escalating (0.6, 2.5, and 10.0 mg/kg) MPD doses. After completion of the last recording, the rat was returned to its home cage. To induce behavioral sensitization, animals were injected for five days with 2.5 mg/kg MPD. Following a rechallenge with saline and identical MPD doses as those given on experimental day 1, locomotor recording of the rat was also performed on experimental days 2, 6 and 11. Results showed that repeated administration of MPD increased locomotion in dose-response manner and elicited behavioral sensitization, while the amplitude of the sensory evoked field responses of the VTA and NAc exhibited dose-response attenuation on both recording days (days 1 and 10). In addition, repeated administration of MPD resulted in attenuating the baseline amplitudes of sensory input on experimental day 10, while MPD administration on experimental day 10 elicited further attenuation of the VTA and NAc sensory evoked responses. Such further attenuation can be interpreted as electrophysiological sensitization.