Acute and chronic methylphenidate alters prefrontal cortex neuronal activity recorded from freely behaving rats

Abstract

Today’s students around the world are striking deals to buy and sell the drug methylphenidate (MPD) for cognitive enhancement. Our knowledge on the effects of MPD on the brain is very limited. The present study was designed to investigate the acute and chronic effect of MPD on the prefrontal cortex (PFC) neurons. On experimental day 1 (ED1) recordings were obtained following saline injections and after 2.5 mg/kg MPD. On ED2 through ED6, daily single 2.5 mg/kg MPD was given followed by 3 washout days (ED7 to 9). On ED10, neuronal recordings were resumed from the same animal after saline and MPD injection similar to that obtained at ED1. Ninety PFC units were recorded, all responded to the initial MPD injection, 66 units (73%) increased their activity At ED10. Recordings were resumed for the 66 units that increased their firing rate at ED1, and following MPD injection 54 units (82%) exhibited significant increases in their baseline firing rates compared to ED1 baseline. When these 54 units were rechallenged (chronic effect) with MPD, 39/54 (72%) exhibited reduction in their firing rate which can be interpreted as tolerance. From the 24 (27%) units that responded to MPD at ED1 by decreasing their activity, 14 units (58%) exhibited a decrease in their baseline firing rates at ED10 compared to ED1 baseline. However, following MPD rechallenge of these 14 units, 11 units (79%) exhibited an increase in their firing rate which is interpreted as sensitization. In conclusion, all PFC units modified their neural baseline activity.

Acute and chronic dose–response effect of methylphenidate on ventral tegmental area neurons correlated with animal behavior

“…When a 3:1 signal to noise ratio spike activity was obtained, the electrode was permanently secured to the skull using web glue cyanoacrylate surgical adhesive. When the neuronal activity exhibited less than a 3:1 signal to noise ratio spike activity, the electrode was lowered in 5-10 μm increments up to a maximum depth of 8.5 mm until a 3:1 ratio activity was observed (Chong et al, 2012; Claussen and Dafny, 2012; Dafny, 1980; 1982; Dafny and Terkel, 1990; Salek et. al., 2012).…”

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

“…These firing rates were subsequently found not to hold normality assumptions, and thus differences in mean firing rates were assessed using the critical ratio (CR) test, wherein CR ϭ ͑E Ϫ C͒ ⁄ ͙ ͓EϩC͔ ϭ Ϯ 1.96 ϭ P Ͻ 0.05 (C ϭ activity following saline [control] injection; E ϭ activity following MPD injection). CR values greater than ϩ1.96 indicate that the treatment elicited a significant increase in neuronal activity, while CR values less than Ϫ1.96 indicate that the treatment elicited a significant decrease in neuronal activity Claussen and Dafny 2012;Salek et al 2012). Three comparisons were made, similar to the behavioral comparisons in Analysis of Behavioral Data: first, the acute effect of MPD was evaluated by comparing day 1 baseline activity with day 1 activity following MPD administration.…”

“…Spike sorting from the recording was conducted using Spike 2.7 software (CED) at sampling rates of up to 200 kHz and processed using low-and high-pass filters (0.3-3 kHz), with two window discriminatory levels accounting for both positiveand negative-going spikes. Spikes were processed as described in previous publications Claussen and Dafny 2012;Claussen et al 2014;Salek et al 2012). The parameters for spike sorting used on data recorded on day 1 from each particular electrode and animal were stored and reused identically on day 10, thus assuring that the spike patterns captured on these days were the same for each particular animal and electrode (see Figs.…”

“…Lastly, the effects of MPD rechallenge on day 10 were compared with the effects elicited following the initial MPD injection on day 1 to determine whether the animal exhibited electrophysiological sensitization (increase in neuronal activity) or tolerance (decrease or no change in neuronal activity). Changes of mean activity induced by MPD treatment were considered statistically significant if the firing rate after treatment differed by at least 2 SE from the mean Dafny 1982;Salek et al 2012).…”

“…In addition, it has been reported that MPD administration in anesthetized animals elicits a decrease in neuronal activity, while nonanesthetized animals exhibit the reverse effect, in that they show an increase in neuronal activity (Ruskin et al 2001). For this reason, nonanaesthetized, freely behaving animals previously implanted with permanent electrodes are used to preclude any influence of anesthetic drugs on electrophysiological measurements Salek et al 2012). The ultimate objective of the present study is to evaluate the MPD dose-response characteristics of NAc neuronal activity recorded in adolescent animals exhibiting behavioral sensitization after acute and repetitive MPD administration separately from animals that express behavioral tolerance after repetitive MPD administration.…”