Methylphenidate (Ritalin) affects serotonin signaling differently in young compared to adults. Concomitant behavioral and neuronal recording from dorsal raphe in freely behaving rats

Abstract

Currently, methylphenidate (MPD) is one of the most commonly prescribed psychostimulants for management and treatment of attention deficit hyperactivity disorder (ADHD). A rise in the consumption of MPD by “ordinary” youth and adults prompted concern regarding the ontogeny effects of acute and chronic MPD exposure. The objective of this study is to concomitantly record behavioral and neuronal activity from the dorsal raphe (DR) nucleus, a major source of serotonergic innervation in the mammalian brain before and following different doses of acute and chronic administration of MPD in freely behaving adolescent (young) and adult rats previously implanted with electrodes in the DR. A wireless recording system over 10 consecutive experimental days was used. Four experimental groups were used: saline, 0.6, 2.5, and 10.0 mg/kg MPD for young and similar groups for adult rats. Animals received one daily MPD injection on experimental days 1-6, followed by three washout days, and then drug rechallenge on experimental day 10 (ED10). 860 DR units were recorded, 356 from adult rats and 504 from young rats. The study provides experimental evidence that the responses to acute and chronic MPD were significantly different between the two age groups. Moreover, the study implies that it is essential to evaluate the electrophysiological responses to a drug based on the animal’s behavioral response to chronic drug exposure and that the DR and serotonin signaling has a significant role in the response to MPD as well as a different role in young as compared to adult rats.