Glutaminergic signaling in the caudate nucleus is required for behavioral sensitization to methylphenidate

Publication date: Available online 19 June 2019Source: Pharmacology Biochemistry and BehaviorAuthor(s): Nicholas King, Samuel Floren, Natasha Kharas, Ming Thomas, Nachum DafnyAbstractMethylphenidate (MPD) is a widely prescribed psychostimulant for the treatment of attention deficit hyperactivity disorder, and is growing in use as a recreational drug and academic enhancer. MPD acts on the reward/motive and motor circuits of the CNS to produce its effects on behavior. The caudate nucleus (CN) is known to be a part of these circuits, so a lesion study was designed to elucidate the role of the CN in response to acute and chronic MPD exposure. Five groups of n = 8 rats were used: control, sham CN lesions, non-specific electrolytic CN lesions, dopaminergic-specific (6-OHDA toxin) CN lesion, and glutaminergic-specific (ibotenic acid toxin) CN lesions. On experimental day (ED) 1, all groups received saline injections. On ED 2, surgeries took place, followed by a 5-day recovery period (ED 3–7). Groups then received six daily MPD 2.5 mg/kg injections (ED 9–14), then three days of washout with no injection (ED 15–17), followed by a re-challenge with the previous 2.5 mg/kg MPD dose (ED 18). Locomotive activity was recorded for 60 min after each injection by a computerized animal activity monitor. The electrolytic CN lesion group responded to the MPD acute and chronic exposures similarly to the control and sham groups, showing an increase in locomotive activity, i.e. sensi...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research