Glutaminergic Signaling in the Nucleus Accumbens Modulates the Behavioral Response to Acute and Chronic Methylphenidate

Abstract

Methylphenidate (MPD) is a psychostimulant that acts on the CNS to produce behavioral effects. The nucleus accumbens (NAc) is involved in this, however the role of the NAc’s glutaminergic system in the behavioral response to MPD has not been studied. Three groups of animals were used: control, sham NAc lesions, and glutaminergic-specific (ibotenic acid toxin) NAc lesion groups. On experimental day (ED) 1, all groups received saline. On ED 2, NAc surgeries took place, followed by a 5-day recovery period (ED 3-7). On ED 8 a post-surgical baseline recording was obtained. Groups then received six daily MPD 2.5 mg/kg injections (ED 9-14) to produce a chronic effect of MPD exposure, behavioral sensitization, then three days of washout (ED 15-17), followed by a re-challenge with 2.5 mg/ kg MPD on ED 18. Locomotive activity was recorded for 60 minutes after each injection. All groups showed an increase in behavioral activity following acute MPD exposure, and developed behavioral sensitization following chronic MPD exposure that was maintained after washout. Compared to NAc intact controls and sham lesions, glutaminergic selective ibotenic acid lesions to the NAc significantly (P<0.05) attenuated the horizontal activity response to both acute and chronic MPD. Glutaminergic selective ibotenic acid lesions to the NAc also resulted in further significant (P<0.05) augmentation of stereotypic activity above the control group. The glutaminergic lesion failed to modulate total distance traveled. This indicates that glutaminergic signaling in the NAc modulates behavioral activity circuits in the NAc differently, and suggests a role in the volitional response to MPD.