Differential changes in mesolimbic dopamine following contingent and non-contingent MDMA self-administration in mice

Abstract

These results suggest that prolonged exposure to MDMA in mice produces changes in basal DA levels after drug withdrawal and a decreased neurochemical response at the level of the mesolimbic DA reward pathway that is, in part, related to instrumental learning during self-administration.

Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

“…The present in vivo microdialysis data are consistent not only with earlier reports for methamphetamine (Stefanski et al, 1999(Stefanski et al, , 2004; but see Stefanski et al, 2002), but also with reports of active-passive distinctions in the development of NAC neurochemical plasticity as derived from studies using animal models of heroin, cocaine or MDMA self-administration (eg, Lecca et al, 2007a b;McFarland et al, 2003;Orejarena et al, 2009).…”

“…Moreover, it is also unclear whether or not the divergent dopamine effects produced by the self-administration of different amphetamine derivatives relate to distinctions in their affinities for the different monoamine transporters, issues related to drug dose or other procedural differences. Nevertheless, while drug dose, route of administration and temporal patterning of drug delivery may certainly contribute to the differential effects of injected vs selfinfused methamphetamine on neurochemical measures and neurotoxicity within the cell body and terminal regions of the mesolimbic and nigrostriatal dopamine systems (see Schwendt et al, 2009;Shepard et al, 2006 for discussion), it is clear from the microdialysis studies conducted to date, in which total daily drug dose/ intoxication levels, route of administration, and/or temporal patterning of drug delivery were similar between groups (Figure 5), that the behavioral contingency of drug delivery is a critical factor influencing the magnitude, time-course and duration of dopamine and glutamate sensitization within the NAC (this study; LaLumiere and Lecca et al, 2007a, b;McFarland et al, 2003;Orejarena et al, 2009;Ranaldi et al, 1999).…”

“…However, it is interesting to note that, in this study, methamphetamine increased dopamine and glutamate responsiveness in animals with a prior history of methamphetamine self-administration compared with those receiving passive IV infusions, while studies of MDMA and d-amphetamine self-administration indicated significantly reduced basal and/or drug-stimulated dopamine release in animals infused contingently vs non-contingently with these amphetamine compounds (Orejarena et al, 2009;Ranaldi et al, 1999). Whether or not the self-administration of these three structurally related stimulants also produces divergent effects on NAC glutamate (or other neurotransmitters) is not known; however, non-contingent administration studies indicate that this might be the case (eg, Nash and Yamamoto, 1992;Shoblock et al, 2003;Yeh et al, 2002).…”

“…Moreover, our microdialysis procedures were conducted by personnel distinct from those involved in self-administration training to further reduce the influence of conditioned factors associated with drug self-administration on neurotransmitter levels. The MDMA self-administration study conducted by Orejarena et al (2009) employed a similar experimental design as that used in this study and also observed activepassive distinctions in basal, as well as, MDMA-induced dopamine release. Thus, while the presence of discrete or contextual cues associated with drug delivery can influence the extent to which a challenge injection of drug elicits neurotransmitter release within the NAC following a history of drug self-administration (eg, Di Ciano et al, 2002), drug-associated conditioning is not likely a major contributing factor to our observed neurochemical differences between METH-SA and METH-NC rats.…”

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

“…Substantial evidence demonstrates that volitional (actively intended) drug intake produces distinct physiological, biochemical, and behavioral effects when compared with forced drug administration. For example, the response contingency of drug exposure robustly influences gene expression (Jacobs et al, 2002(Jacobs et al, , 2003(Jacobs et al, , 2005, neural activation (Chang et al, 1994;Peoples and West, 1996;Stuber et al, 2005), and resultant extracellular neurochemistry (Di Ciano et al, 1996;Hemby et al, 1997;Jacobs et al, 2003;Lecca et al, 2007;Orejarena et al, 2009;You et al, 2007). With specific regard to nicotine, differential effects of volitional SA vs forced drug administration have been observed on a 4 b 2 nAChR expression (Metaxas et al, 2010), cortical glutamatergic projection activity and plasticity mechanisms in the ventral tegmental area (VTA) (McFarland et al, 2003;You et al, 2007), and plasma corticosterone levels (Donny et al, 2000).…”