Mesolimbic dopamine in desire and dread: enabling motivation to be generated by localized glutamate disruptions in nucleus accumbens - PubMed (original) (raw)

Mesolimbic dopamine in desire and dread: enabling motivation to be generated by localized glutamate disruptions in nucleus accumbens

Alexis Faure et al. J Neurosci. 2008.

Abstract

An important issue in affective neuroscience concerns the role of mesocorticolimbic dopamine systems in positive-valenced motivation (e.g., reward) versus negative-valenced motivation (e.g., fear). Here, we assessed whether endogenous dopamine receptor stimulation in nucleus accumbens contributes to both appetitive behavior and fearful behavior that is generated in keyboard manner by local glutamate disruptions at different sites in medial shell. 6,7-Dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) microinjections (450 ng) locally disrupt glutamate signals in <4 mm(3) of nucleus accumbens, and generate either desire or fear (or both) depending on precise rostrocaudal location in medial shell. At rostral shell sites, local AMPA/kainate blockade generates positive ingestive behavior, but the elicited motivated behavior becomes incrementally more fearful as the same microinjection is moved caudally. A dopamine-blocking mixture of D(1) and D(2) antagonists (raclopride and SCH-23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benzazepine hydrochloride]) was combined here in the same microinjection with DNQX to assess the role of endogenous local dopamine in mediating the DNQX-motivated behaviors. We report that local dopamine blockade prevented DNQX microinjections from generating appetitive behavior (eating) in rostral shell, and equally prevented DNQX from generating fearful behavior (defensive treading) in caudal shell. We conclude that local dopamine is needed to enable disruptions of corticolimbic glutamate signals in shell to generate either positive incentive salience or negative fearful salience (valence depending on site and other conditions). Thus, dopamine interacts with localization of valence-biased glutamate circuits in medial shell to facilitate keyboard stimulation of both appetitive and fearful motivations.

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Figures

Figure 1.

Colored plume maps show average local elevations of Fos caused by microinjection of DNQX, relative to vehicle (top left). DNQX caused robust plumes of up to a 4 mm3 volume, elevated 200 to 400% above vehicle levels. The DNQX minus mixture reduction map (top right) shows the average suppression of DNQX-induced Fos caused by addition of DA antagonists to same microinjection. Examples of Fos plumes produced by DNQX, vehicle, and mixture microinjections are shown in photomicrographs (bottom left, center, and right, respectively). Stars denote placements of cannula tips.

Figure 2.

A, B, Fos plume maps of appetitive eating behavior versus fearful defensive treading behavior generated by DNQX and mixture microinjections. Each plume-sized circle represents color-coded behavioral effects of DNQX or mixture at that site, compared with vehicle control levels at same site in the same rat (expressed by the color scale as a change score). Left maps show the behavioral effects of pure DNQX microinjections. Right maps show the effects of mixture microinjections (D1 antagonist plus D2 antagonist plus DNQX). A, Appetitive behavior (food intake). B, Fearful behavior (defensive treading). Histograms above or next to graphs represent rostrocaudal or dorsoventral levels showing the mean behavioral effects produced by microinjections at each level (expressed as a change score from vehicle microinjection at the same site in the same rat; +SEM). Sagittal sections are adapted from Paxinos and Watson (2004).

Figure 3.

A, B, Magnitude of increases in food intake (A) and defensive treading (B) behaviors elicited by DNQX, mixture, dopamine antagonists alone, or vehicle microinjections in the anterior and posterior halves of the medial shell of the nucleus accumbens. Data are shown from both the primary test group [DNQX, mixture (DNQX plus dopamine antagonist), and DMSO/saline vehicle] and an additional control group (dopamine antagonists alone, DMSO/saline vehicle, pure saline vehicle. *p < 0.05; **p < 0.01; #p < 0.05, anterior versus posterior. Error bars indicate SEM.

Figure 4.

Summary map of “desire versus dread” motivations produced by microinjections of DNQX versus mixture (D1/D2/DNQX). Appetitive eating behavior (green symbols) was stimulated by DNQX microinjections in the rostral shell, whereas fearful defensive treading was elicited by caudal DNQX microinjections (red symbols; criteria for including a DNQX site was a >9 min increase in eating duration plus a >200% increase in food intake for appetitive effects, and >20 s duration and >400% increase in defensive treading behavior; both compared with vehicle microinjection at same site). Histogram bars express the percentage change in behaviors from vehicle levels [eating duration (in minutes); defensive treading duration (in seconds)]. Addition of D1 and D2 receptor antagonists in the mixture condition blocked the ability of DNQX to generate either eating or defensive behavior at most sites (right).

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Mesolimbic dopamine in desire and dread: enabling motivation to be generated by localized glutamate disruptions in nucleus accumbens - PubMed (original) (raw)