Neither ibotenic acid nor volkensin lesions of the nucleus accumbens shell affect the expression of cocaine sensitization

Abstract

Studies have shown that the nucleus accumbens shell plays an integral role in the expression of psychostimulant-induced behavioural sensitization. Dopaminergic regulation of excitatory amino acid inputs in this region of the brain could be a key factor in the neural influence of this phenomenon. Alterations in the dopaminergic innervation patterns in the shell have been demonstrated in rats that received repeated cocaine injections. Furthermore, lesions of brain regions that send projections to the shell alter psychostimulant-induced locomotion, both acutely and in sensitization paradigms. A previous study from our laboratory demonstrated that lesions of the shell before repeated cocaine treatment decrease the locomotor response to cocaine during the induction phase of behavioural sensitization. To better understand the role of this brain region during the expression phase of behavioural sensitization, the present study examined the effects of two forms of cytotoxic lesions of the shell. Rats received a sensitization-inducing regimen of cocaine (bi-daily injections of 15 mg/kg i.p. for 5 consecutive days). Two days after the last injection, rats demonstrating behavioural sensitization received one of three bilateral microinjections into the shell: (i) 0.5 micro L 0.9% saline; (ii) 2.5 micro g/0.5 micro L ibotenic acid (which lesions the cell bodies at the injection site); or (iii), 0.5 ng/0.2 micro L of volkensin (a retrograde suicide transport lectin). Upon challenge with cocaine (15 mg/kg) 12 days after surgery, neither ibotenic acid- nor volkensin-lesioned rats showed any difference in their locomotor response compared with sham controls. These data indicate that bilateral shell lesions do not affect the long-term expression of behavioural sensitization in cocaine-sensitized rats.

The Role of Glutamate Receptor Redistribution in Locomotor Sensitization to Cocaine

“…It should be emphasized that our experiments were designed to test the hypothesis that enhanced AMPAR surface expression is required for the expression of locomotor sensitization, not to determine if there is an absolute requirement for some level of AMPAR transmission. Finally, it is important to note that our CNQX infusions into the NAc core do not address the role of AMPAR transmission in the NAc shell in the expression of sensitization (but see Todtenkopf et al, 2002) or the role of AMPAR transmission in the DS.…”

Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core

“…On the one hand, psychostimulant sensitization-induced long-term changes in cellular reactivity or cellular morphology are not generally found in the nucleus accumbens shell after psychostimulant administration (Cadoni et al 2000 ; Li et al 2004 ; Todtenkopf et al 2002a ). Moreover, post induction lesions of the shell leave the expression of cocaine sensitization intact (Todtenkopf et al 2002b ), although preinduction lesions of a subarea of the shell result in reduced sensitized, but not acute responses to cocaine (Brenhouse and Stellar 2006 ). On the other hand, microinjection of amphetamine or cocaine into the shell (but not core) produces sensitized psychomotor responses and augmented dopamine levels in animals pretreated with cocaine (Filip and Siwanowicz 2001 ; Pierce and Kalivas 1995 ), and sensitized cellular reactivity has been observed in specific subareas within the accumbens shell after repeated cocaine administration (Brenhouse et al 2006 ; Todtenkopf et al 2002a ).…”

“…However, the lack of sensitization of c- fos expression in the medial prefrontal cortex corresponds well with results from other groups showing similar results after 2 weeks of abstinence (Todtenkopf et al 2002a ). Sensitization of c- fos immunoreactivity does occur when animals are challenged after 2 days of abstinence (Hedou et al 2002 ; Todtenkopf et al 2002a , b ), suggesting a role in the induction or early phases of sensitization. In support of a role for the prefrontal cortex in the induction and early phases of expression, lesion studies have demonstrated region-specific effects in the involvement of prefrontal areas in the induction of cocaine sensitization (Tzschentke and Schmidt 2000 ), and lesions of the entire medial prefrontal cortex have been shown to prevent the induction of amphetamine sensitization (Wolf et al 1995 ; Cador et al 1999 , but see Tzschentke and Schmidt 2000 ).…”

AMPA receptor plasticity in the nucleus accumbens after repeated exposure to cocaine

“…CNQX is a competitive antagonist, so its efficacy might be influenced by procedural differences that alter the level of cocaine-induced glutamate release in the NAc. Other differences between the studies (e.g., withdrawal time) may also contribute to the discrepancy (see Ferrario et al, 2010 for more discussion) and it is notable that none of the CNQX studies targeted the shell (but see Todtenkopf et al, 2002). Nevertheless, given that CNQX certainly produced some reduction of AMPAR occupancy, our results suggest that one can reduce AMPAR occupancy in the core without affecting the magnitude of the sensitized locomotor response.…”