Behavioral sensitization and cross-sensitization between methylphenidate amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in female SD rats

Abstract

The psychostimulants amphetamine and methylphenidate (MPD / Ritalin) are the drugs most often used to treat attention deficit hyperactivity disorder (ADHD). In addition, students of all ages take these drugs to improve academic performance but also abuse them for pleasurable enhancement. In addition, other psychostimulants such 3,4 methylenedioxymethamphetamine (MDMA / ecstasy) are used / abused for similar objectives. One of the experimental markers for the potential of a drug to produce dependence is its ability to induce behavioral sensitization and cross sensitization with other drugs of abuse. The objective of this study is to use identical experimental protocols and behavioral assays to compare in female rats the effects of amphetamine, MPD and MDMA on locomotor activity and to determine if they induce behavioral sensitization and/or cross sensitization with each other. The main findings of this study are 1. Acute amphetamine, MPD and MDMA all elicited increases in locomotor activity. 2. Chronic administration of an intermediate dose of amphetamine or MPD elicited behavioral sensitization. 3. Chronic administration of MDMA elicited behavioral sensitization in some animals and behavioral tolerance in others. 4. Cross sensitization between MPD and amphetamine was observed. 5. MDMA did not show either cross sensitization or cross tolerance with amphetamine. In conclusion, these results suggest that MDMA act by different mechanisms compared to MPD and amphetamine.

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

“…The open field system 16 and 8 infrared beams and their sensors on the opposite side set at 5 cm above the floor of the cage. The open field assay has been previously described in detail (Gaytan et al, 1996, 1997a, b, 2000; Yang et al, 2006a, 2007, 2011). In short, the activity monitoring system checked each of the sensor beams at a 100 Hz frequency to determine whether beams were interrupted.…”

“…Tolerance to a drug refers to drug induced adaptations that lead to attenuating effects when the same dose of that drug is given again; to get the same effect, a higher dose is required. Alternatively, behavioral sensitization is a progressive amplification of behavioral responses to repeated psychostimulant exposure (Chao and Nestler, 2004; Dafny and Yang 2006; Gaytan et al, 1996; Kalivas et al, 1988; Lee et al, 2009; Robinson 1984; Wolf 1988; Yang et al, 2003, 2011). Behavioral tolerance and sensitization are experimental markers used to indicate the potential of a psychostimulant to elicit drug dependence.…”

“…(Kalivas et al, 1998; Kauer, 2004; Nestler, 2005). It has been shown that stimulants like cocaine, amphetamine, and MPD cause dose dependent behavioral sensitization in animals (Algahim et al, 2009; Bergheim et al, 2012; Gaytan et al, 1996, 1999; Kalivas et al, 1988; Tang et al, 2009; Yang et al, 2003, 2011). Using behavioral and pharmacological assays, it was proposed that behavioral sensitization exhibits two phases, induction and expression (Kalivas and Stewart, 1991).…”

“…Different responses to the same dose of MPD across individuals and ADHD patients have been reported (Volkow and Swanson, 2003) and behavioral tolerance and sensitization to repetitive MPD exposure was reported (Gaytan et al, 1996; Barron et al, 2009; Yang et al, 2003, 2007, 2011). The hypothesis of this study is that the same chronic exposure of MPD dose will elicit behavioral tolerance in some animals and behavioral sensitization in other animals and that the VTA neuronal population activity recorded from animals expressing behavioral tolerance to chronic MPD exposure will respond differently to MPD compared to VTA neuronal population activity recorded from animals expressing behavioral sensitization.…”

Influence of sensitization on the discriminative stimulus effects of methylphenidate in mice

“…In experimental settings, psychostimulant sensitization is commonly demonstrated as increased locomotor activity following repeated exposures to the drug. Several reports indicate that repeated exposure to MPH induces locomotor sensitization in rodents (Askenasy et al , 2007; Yang et al , 2011; Yang et al , 2007). …”