1 2 3 4 5 Behavioral and

39 The nucleus accumbens (NAc) has been shown to play a key role in the brain’s response to methylphenidate 40 (MPD). The present study focuses on neuronal recording from this structure. The study postulates that repetitive 41 exposure to the same dose of MPD will elicit in some rats behavioral sensitization and in others tolerance. 42 Furthermore, the study postulates that NAc neuronal activity recorded from animals expressing behavioral 43 tolerance after repetitive MPD exposure will be significantly different from NAc neuronal activity recorded from 44 animals expressing behavioral sensitization after repetitive MPD exposure at doses of 0.6, 2.5, 5.0, and 10.0 mg/kg. 45 To test this, behavioral and neuronal activity was recorded concomitantly from the NAc of freely behaving 46 adolescent rats (P-40) before and after acute and repetitive administration of four different MPD doses. Comparing 47 the acute MPD effect to the repetitive MPD effect revealed that the acute response to MPD exhibited dose response 48 characteristics: an increase in behavioral activity correlated with increasing MPD doses. On the other hand, 49 following repetitive MPD exposure, some animals exhibited attenuated behavior (tolerance), while others 50 exhibited further increases in the recorded behavior (sensitization). Moreover, the neuronal activity following 51 repetitive MPD exposure recorded in animals exhibiting behavioral sensitization was significantly different from 52 neuronal activity recorded in animals exhibiting behavioral tolerance. This implies that when studying the effects 53 of repetitive MPD administration on adolescent rats, it is advisable to simultaneously record both neuronal and 54 behavioral activity, and to evaluate all data based on the animals' behavioral response to the repetitive MPD 55 exposure. 56 57