Nachum Dafny
The University of Texas Medical School at Houston, Washington
Title: Methylphenidate Modulates Dorsal Raphe Neuronal Activity: Behavioral and Neuronal Recordings from Adolescent Rats.
Biography
Biography: Nachum Dafny
Abstract
Methylphenidate (MPD) is one of the most widely prescribed psychostimulants for the treatment of attention deficit hyperactive disorder (ADHD) in children and adults. MPD binds to presynaptic catecholamine transporters in the CNS and prevents reuptake of norepinephrine and dopamine from the synaptic cleft. Unlike the psychostimulants cocaine and amphetamine, MPD does not exhibit direct actions on the serotonin transporter. Studies investigating MPD tend to focus on its effects on the CNS dopamine circuit, however there is evidence suggesting that MPD affects the serotonergic system as well. This study aimed to investigate the role of the dorsal raphe, a major source of serotonergic innervation in the mammalian brain, in the response to acute and chronic MPD exposure. The hypothesis of the study is 1) the dorsal raphe (DR) participates in MPD action, 2) the same chronic MPD dose in some adolescent animals will elicit behavioral sensitization and in others behavioral tolerance and 3) the DR neuronal activity recorded from adolescent animals expressing behavioral sensitization to chronic MPD will have a significantly different response to MPD exposure than those DR neurons recorded from animals expressing behavioral tolerance to chronic MPD. Freely behaving animals previously implanted bilaterally with permanent electrodes were used. Behavioral and DR electrophysiological activity were concomitantly recorded following acute and chronic MPD exposure using an open field assay and a wireless recording system over 10 experimental days. Four groups of animals were used: one control group (saline) and three experimental groups treated with 0.6, 2.5, and 10.0 mg/kg MPD respectively. The animals received daily MPD or saline injections on experimental days 1-6, followed by 3 washout days and MPD rechallenge dose on experimental day (ED)10. The same chronic dose of MPD resulted in either behavioral sensitization or tolerance. DR neurons responded to acute MPD in a dose dependent manner. Neuronal activity recorded from the DR units of rats expressing behavioral sensitization to chronic MPD exposure exhibited a significantly (p < .05) different response to MPD rechallenge on ED10 compared to the DR neuronal activity recorded from animals that expressed behavioral tolerance to chronic MPD. This correlation between behavioral response and DR neuronal activity following chronic MPD exposure indicates that the DR is involved at least in part in the acute effects of MPD as well as the chronic effects of MPD (expression of sensitization and tolerance) in adolescent rats. The study confirms our hypothesis.