Caudate nucleus neurons participate in methylphenidate function: Behavioral and neuronal recordings from freely behaving adolescent rats.

Methylphenidate (MPD) is the most commonly prescribed psychostimulant for the treatment of attention-deficit hyperactivity disorder (ADHD). MPD acts on brain structures of the reward/motivation system, including the caudate nucleus (CN). The objective of this study was to investigate the acute and chronic dose response effects of MPD on CN neurons in freely behaving adolescent rats. Semi-microelectrodes were implanted into the CN of one hundred and sixty-three adolescent male Sprague-Dawley rats. On experimental day one (ED1), each rat was injected with 0.8 ml saline followed by an injection of MPD (0.6, 2.5, or 10.0 mg/kg). Behavioral and neuronal recordings of 60 min followed each injection. Throughout ED2-6, each rat remained in its home cage and received daily injections of a specific dose of MPD. ED7-9 consisted of a three-day washout period during which no injections were given. On the last day (ED10), each rat was returned to the testing chamber in its home cage and an identical protocol was performed as on ED1. The same repetitive (i.e. chronic) dose of MPD elicited behavioral sensitization in some animals and behavioral tolerance in others. After chronic MPD exposure, CN units recorded from rats expressing behavioral sensitization responded mainly with increased neuronal firing rates. Conversely, rats expressing behavioral tolerance responded mainly with decreased neuronal firing rates. These findings suggest a direct correlation between the behavioral and CN neurophysiological response to chronic MPD in adolescent animals. Published by Elsevier Inc.