Behavioral and locus coeruleus neuronal activity following acute and chronic methylphenidate in freely behaving adolescent rats
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Acute and chronic methylphenidate (MPD) administration was recorded simultaneously in freely moving adolescent rats previously implanted with permanent semi-microelectrodes using telemetric wireless technology for the rat's locomotor activity and for the locus coeruleus (LC) neuronal activity. The evaluation of neuronal events was separated based on the rat's behavioral response to chronic MPD exposure, with rats eliciting behavioral sensitization or behavioral tolerance. On experimental day (ED) 1, the locomotor and neuronal activity was recorded after saline (baseline) and MPD (0.6, 2.5, or 10.0 mg/kg) injection (i.p.). The rats were administered daily with a single dose of MPD for five consecutive days (ED2-ED6) to elicit behavioral sensitization or behavioral tolerance. Following three washout days with no drugs, the locomotor and neuronal activity recordings resumed on ED10 post saline and rechallenge MPD administration. The main findings were as follows. The same dose of chronic MPD administration elicited behavioral sensitization in some rats and behavioral tolerance in other rats. A total of 51.5%, 56.6%, and 86.3% of LC units responded significantly to acute 0.6, 2.5, and 10.0 mg/kg MPD respectively. A total of 51.5%, 72.4%, and 82.3% of LC units responded significantly by changing their baseline activity on ED10 compared to that on ED1 in 0.6, 2.5, and 10.0 mg/kg MPD dose groups respectively. A total of 53%, 67.1%, and 90.2% of LC units responded significantly to chronic 0.6, 2.5, and 10.0 mg/kg MPD respectively. The LC neuronal population recording following acute MPD on ED1 and rechallenge MPD on ED10 from the rats eliciting behavioral sensitization was significantly different from the neuronal population recorded from the rats eliciting behavioral tolerance. Overall, these findings show that the same dose of chronic MPD can elicit behavioral sensitization or behavioral tolerance. We were able to verify our hypothesis that the LC units recorded from the rats eliciting behavioral sensitization responded significantly different to MPD from the rats eliciting behavioral tolerance. This correlation suggests that LC neuronal activity plays an important role in the expression of behavioral sensitization and behavioral tolerance by chronic MPD exposure.