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.

Comparison of the VTA and LC response to methylphenidate: a concomitant behavioral and neuronal study of adolescent male rats.

Methylphenidate (MPD), also known as Ritalin, is a psychostimulant used to treat attention deficit hyperactivity disorder. However, it is increasingly being misused by normal adolescents for recreation and academic advantage. Therefore, it is important to elucidate the behavioral and neurophysiological effects of MPD in normal subjects. MPD inhibits the reuptake of catecholamines, mainly found in the ventral tegmental area (VTA) and locus coeruleus (LC). The VTA and LC normally mediate attention, motivation, and drug reward behaviors. Selective neuronal connections between the VTA and LC have been identified implicating regular interaction between the structures. The objective of this study was to compare the neuronal responses of the VTA and LC to MPD in normal adolescent rats. Animals were implanted with permanent electrodes in the VTA and LC, and neuronal units were recorded following acute and repetitive (chronic) saline or 0.6, 2.5, or 10.0 mg/kg MPD exposure. Animals displayed either behavioral sensitization or tolerance to all three doses of MPD. Acute MPD exposure elicited excitation in the majority of all VTA and LC units. Chronic MPD exposure elicited a further increase in VTA and LC neuronal activity in animals exhibiting behavioral sensitization and an attenuation in VTA and LC neuronal activity in animals exhibiting behavioral tolerance, demonstrating neurophysiological sensitization and tolerance, respectively. The similar pattern in VTA and LC unit activity suggests that the two structures are linked in their response to MPD. These results may help determine the exact mechanism of action of MPD, resulting in optimized treatment of patients.NEW & NOTEWORTHY The same dose of 0.6, 2.5, and 10 mg/kg methylphenidate (MPD) elicits either behavioral sensitization or tolerance in adolescent rats. There is a direct correlation between the ventral tegmental area (VTA) and locus coeruleus (LC) neuronal response to chronic MPD exposure. Both the VTA and LC are involved in the behavioral and neurophysiological effects of chronic MPD.