Effects of intranucleus accumbens shell administration of dopamine agonists and antagonists on cocaine-taking and cocaine-seeking behaviors in the rat

Abstract

Both D(1) and D(2) receptors in the NAc play a prominent, and perhaps cooperative, role in regulating cocaine-taking and cocaine-seeking behaviors.

Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell

“…Indeed, Veeneman et al (2012) attributed to NAc shell DA the motivational role that Bari and Pierce (2005) and Di Ciano (2008) attributed to NAc core DA. It is notable however, that in the study of Veeneman et al (2012), in order to infuse flupentixol in the ventro-medial shell, cannulas went through the dorsally located core, while in the studies of Bari and Pierce (2005), Bachtell et al (2005) and Di Ciano (2008), as well as in the present study, the medio-dorsal part of the shell was targeted, thus sparing the core. In order to explain the above discrepancies, one might consider that in the study of Veeneman et al (2012), flupentixol may have reached the dorsally located core by leakage of the fluid along the track that the cannula left in the core on its way to the shell.…”

“…Infusion of flupentixol into the core had no effect. The observations of Veeneman et al (2012) are at odds with those of Bari and Pierce (2005) (no effect of intra-shell DA antagonists on food reinforcement) and with those of Bachtell et al (2005) and Di Ciano (2008) (increase in responding for i.v. cocaine after intra-shell DA antagonists).…”

“…To our knowledge, four studies have directly compared the effect of impairment of DA transmission in the NAc shell and core on cocaine reinforcement. While in two studies no clear-cut differences were obtained between the two NAc subdivisions (Bachtell et al, 2005;Bari and Pierce, 2005), in the other two studies, the differences obtained have led to opposite conclusions (Di Ciano, 2008;Veeneman et al, 2012). These discrepancies and inconsistencies might result from the use of local intracerebral infusion of DA antagonists as a tool to manipulate DA transmission in the NAc shell and core.…”

Addiction-Related Alterations in D1 and D2 Dopamine Receptor Behavioral Responses Following Chronic Cocaine Self-Administration

“…Together, these studies suggest that D 2 receptors could play a major role in eliciting relapse to cocaine seeking when environmental stimuli such as cocaine-related cues or stress activate the mesolimbic dopamine system (Phillips et al, 2003;Pruessner et al, 2004), while D 1 receptor tone may provide inhibitory regulation over cocaine seeking. In contrast to agonists, both D 1 and D 2 receptor antagonists block reinstatement of cocaine seeking in rats (Weissenborn et al, 1996;Ciccocioppo et al, 2001;Norman et al, 2002;Vorel et al, 2002;Schenk and Gittings, 2003;Gilbert et al, 2005), and indiscriminately block the reinstating effects of nucleus accumbens agonist administration (Bachtell et al, 2005), consistent with well-characterized enabling and synergistic interactions between D 1 and D 2 receptors on behavioral responses (Waddington and Daly, 1993).…”

“…In addition, levels of cocaine exposure that produce supersensitive D 1 -mediated physiological responses in nucleus accumbens neurons are more similar to levels in low than high intake animals in our study. However, it should be noted that nucleus accumbens infusions of D 1 agonists induce rather than inhibit reinstatement of cocaine seeking, suggesting that widespread D 1 receptor activation in multiple or other brain regions is required for satiation of cocaine seeking by systemic D 1 agonist administration (Bachtell et al, 2005).…”