Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the "shell" as compared with the "core" of the rat nucleus accumbens.

Abstract

The nucleus accumbens is considered a critical target of the action of drugs of abuse. In this nucleus a "shell" and a "core" have been distinguished on the basis of anatomical and histochemical criteria. The present study investigated the effect in freely moving rats of intravenous cocaine, amphetamine, and morphine on extracellular dopamine concentrations in the nucleus accumbens shell and core by means of microdialysis with vertically implanted concentric probes. Doses selected were in the range of those known to sustain drug self-administration in rats. Morphine, at 0.2 and 0.4 mg/kg, and cocaine, at 0.5 mg/kg, increased extracellular dopamine selectively in the shell. Higher doses of cocaine (1.0 mg/kg) and the lowest dose of amphetamine tested (0.125 mg/kg) increased extracellular dopamine both in the shell and in the core, but the effect was significantly more pronounced in the shell compared with the core. Only the highest dose of amphetamine (0.250 mg/kg) increased extracellular dopamine in the shell and in the core to a similar extent. The present results provide in vivo neurochemical evidence for a functional compartmentation within the nucleus accumbens and for a preferential effect of psychostimulants and morphine in the shell of the nucleus accumbens at doses known to sustain intravenous drug self-administration.

Differential Regulation of the Mesoaccumbens Dopamine Circuit by Serotonin2C Receptors in the Ventral Tegmental Area and the Nucleus Accumbens: An In Vivo Microdialysis Study with Cocaine

“…In agreement with previous reports (Andrews and Lucki, 2001;Bubar et al, 2003;Navailles et al, 2004;Pontieri et al, 1995), the systemic administration of cocaine elicited a significant increase in DA extracellular levels in the NAc. As suggested by Fletcher et al (2004), we found that cocaineinduced DA outflow was dose-dependently inhibited by the intra-VTA injection of the 5-HT 2C R agonist Ro 60-0175.…”

Reduced Dopamine Terminal Function and Insensitivity to Cocaine Following Cocaine Binge Self-Administration and Deprivation

“…One idea is that the shell mediates the rewarding effects of drugs of abuse while the core mediates the locomotor stimulant effects (Carlezon and Wise, 1996;Ikemoto et al, 1997;Boye et al, 2001;Sellings and Clarke, 2003). Cocaine and amphetamine appear to preferentially increase glucose utilization in the shell compared with the core of the Nac, and morphine, nicotine, cocaine, and amphetamine preferentially increased extracellular DA in the shell over the core (Pontieri et al, 1995(Pontieri et al, , 1996. In contrast, a number of papers suggest a preferential involvement of the NAc core in morphological changes associated with sensitization (Li et al, 2004), acquisition of opiate SA (Alderson et al, 2001;Hutcheson et al, 2001), and with relapse to cocaine use (McFarland and Kalivas, 2001).…”

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

“…The shell of the nucleus accumbens is also the main terminal area of the mesolimbic dopaminergic brain reward system and has been implicated in motivational and reinforcing effects of drugs abused by humans (Alheid and Heimer, 1988;Heimer et al, 1991;Pontieri et al, 1995). Many drugs abused by humans, including methamphetamine, share the common property of preferentially increasing dopamine release in the shell of the nucleus accumbens (Di Chiara et al, 1999).…”

“…catheters and dialysis probes in the shell of the nucleus accumbens, as described previously (Pontieri et al, 1995;Tanda et al, 1997). Under Equithesin anesthesia, rats were first implanted with i.v.…”

“…Recently, however, it has been shown that these receptors are widely distributed on nonhistaminergic neurons and their activation can inhibit synthesis and release of other neurotransmitters, including dopamine, norepinephrine, GABA, and acetylcholine (Leurs et al, 1998). Histamine H3 receptors are particularly abundant in dopaminergic areas of the brain such as the nucleus accumbens in animals (Lovenberg et al, 1999;Pollard et al, 1993) and humans (Goodchild et al, 1999), the main terminal area of the mesolimbic dopamine system which plays a prominent role in the reinforcing/rewarding effects of methamphetamine and other psychomotor stimulant drugs abused by humans (Wise, 1987;Koob, 1992;Pontieri et al, 1995).…”