Behavioral and neuronal recording of the nucleus accumbens in adolescent rats following acute and repetitive exposure to methylphenidate

Abstract

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

Methylphenidate modulates dorsal raphe neuronal activity: Behavioral and neuronal recordings from adolescent rats

“…Acute injection of 0.6, 2.5, or 10.0 mg/kg on ED1 significantly increased locomotor activity in all test groups in a dose response characteristic. This is consistent with previous studies using the same MPD dosages (Claussen et al, 2014; Frolov et al, 2015). Following 6 daily MPD injections and 3 washout days, the animals received a rechallenge MPD dose on ED10.…”

“…Repetitive exposure to psychostimulants has been shown to elicit dose dependent behavioral tolerance or sensitization (Lee et al, 2014; Frolov et al, 2015) and it is this behavioral outcome that predicts drug abuse liability (Robinson and Berridge, 2001). Behavioral sensitization or tolerance is a phenomenon characterized by a further increased or decreased response to repeated drug exposure compared to the initial (acute) effect respectively (Claussen et al, 2014; Jones et al, 2014).…”

“…Studies suggest that 5HT transmission is involved in the modification of gene regulation by psychostimulants and in the formation of addictive behaviors (Bhat and Baraban, 1993; Andersen et al, 2002; Van Waes et al, 2010). Paradoxically, chronic exposure to identical doses of MPD has been shown to elicit behavioral sensitization in some animals and tolerance in others (Frolov et al, 2015; Jones et al, 2014) however the reason for this dichotomy in adult rats is unclear.…”

Methylphenidate dose–response behavioral and neurophysiological study of the ventral tegmental area and nucleus accumbens in adolescent rats

“…The main behavioral findings of this study were that the same chronic dose of 0.6, 2.5, and 10.0 mg/kg methylphenidate elicited in some animals behavioral sensitization, and in others behavioral tolerance. This is comparable to observations using similar protocols (Claussen & Dafny,; Frolov et al, ;Jones & Dafny, ; Tang & Dafny, ; Venkarataman, Claussen, Joseph, & Dafny, ). In general, the ventral tegmental area and nucleus accumbens units responded to MPD with dose‐response characteristics: with increased MPD dosage more units responded to the drug, from less than 50% of units responding following acute 0.6 mg/kg MPD exposure to more than 70% of units responding following acute 10.0 mg/kg MPD exposure.…”

“…For the second comparison, determining whether repetitive (chronic) saline or methylphenidate injections for six consecutive days with three washout days altered ED10 BL activity, ED1 BL was the control (C) and ED10 BL was the activity after drug exposure (E), so . For the third comparison, determining if sensitization or tolerance had been expressed, ED1 MPD was the control (C) and ED10 MPD was the activity after drug exposure (E), so (Dafny, ; Claussen & Dafny, ; Salek et al ., ; Frolov et al ., ). Behavioral sensitization was considered to be expressed when the animal displayed a significant increase in locomotor activity following chronic methylphenidate exposure on experimental day 10 compared to the initial methylphenidate exposure on experimental day 1.…”