Psychostimulant treatment for ADHD is modulated by prefrontal cortex manipulation

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

“…This was interpreted as behavioral sensitization. The results obtained are similar to those reported by others (Gaytan et al, 1997; Sripada et al, 1998, Tang, 2009). Amphetamine binds to presynaptic membranes, converting all monoamine transporters, particularly dopamine and norepinephrine (Weinshenker et al, 2002) into open dopamine and norepinephrine channels, thus allowing efflux of dopamine and norepinephrine (Vanderschuren et al, 1999 a and b).…”

“…Results from our current and previous behavioral studies indicate that repeated administration of 0.6 mg/kg amphetamine elicits augmented locomotor responses in rats (Gaytan et al, 1998, 1999; Tang et al, 2009). Similar to the effects seen with MPD, there were dose dependent increases in all four indicies of activity on ED2 in comparison to ED1 (see Table 1).…”

“…This suggestion is based on experiments that showed a glutamate antagonist, such as MK-801, blocked the induction of sensitization to amphetamine (Pacchioni et al, 2002). Moreover, destruction of medial prefrontal cortex glutamatergic afferents blocked both the induction and the expression of sensitization following chronic amphetamine administration (Cador et al 1999; Tang et al, 2009). These observations suggest that glutamatergic inputs are necessary to amphetamine effect not only for the induction phase, but also for the expression phase as well.…”

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

“…(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).…”

“…Both DA and GABA neurons in the VTA get input mediated by GABA and glutamate; those afferents containing glutamate come from the PFC, while those of GABA originate in the NAc (Beckstead et al, 1979; Johnson and North, 1992; Kalivas and Duffy, 1995). The dopaminergic neurons in the VTA co-express GABA-ergic or glutamatergic markers and it is thought that these DA neurons are activated by the glutamatergic inputs originating in the PFC and are involved with the induction of behavioral sensitization following repetitive exposure of psychostimulants (Scheggi et al, 2002; Tang et al, 2009; Wanchoo et al, 2010). In a morphological study, it has been shown that about two-thirds of the neurons in the VTA are dopaminergic, while the remaining neurons are mostly GABA (Nair-Roberts et al, 2008).…”