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, 26 (1-2), 200-16

Nucleus Accumbens Core and Pathogenesis of Compulsive Checking

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Nucleus Accumbens Core and Pathogenesis of Compulsive Checking

Javier Ballester González et al. Behav Pharmacol.

Abstract

To investigate the role of the nucleus accumbens core (NAc) in the development of quinpirole-induced compulsive checking, rats received an excitotoxic lesion of NAc or sham lesion and were injected with quinpirole (0.5 mg/kg) or saline; development of checking behavior was monitored for 10 biweekly tests. The results showed that even after the NAc lesion, quinpirole still induced compulsive checking, suggesting that the pathogenic effects produced by quinpirole lie outside the NAc. Although the NAc lesion did not prevent the induction of compulsive checking, it altered how quickly it develops, suggesting that the NAc normally contributes toward the induction of compulsive checking. Saline-treated rats with an NAc lesion were hyperactive, but did not develop compulsive checking, indicating that hyperactivity by itself is not sufficient for the pathogenesis of compulsive checking. It is proposed that compulsive checking is the exaggerated output of a security motivation system and that the NAc serves as a neural hub for coordinating the orderly activity of neural modules of this motivational system. Evidence is considered suggesting that the neurobiological condition for the pathogenesis of compulsive checking is two-fold: activation of dopamine D2/D3 receptors without concurrent stimulation of D1-like receptors and long-term plastic changes related to quinpirole-induced sensitization.

Figures

Fig. 1
Fig. 1
Effects of chronic treatment with quinpirole (QNP) on the criteria measures for compulsive checking (a–d) and on the measure of postchecking satiety (e). See Table 1 for parameters of the indicated regression lines. Each symbol is the mean value for the indicated dependent variable at the indicated injection obtained from all rats showing a value. Note that the parameters of the indicated regression lines were not obtained using these actual means, but were computed from the regression parameters of each individual rat as described in the Materials and methods. Open circles, sham-control group injected repeatedly with saline (sham-saline group); open squares, sham group injected repeatedly with QNP (sham-QNP group); solid circles, nucleus accumbens core (NAc) lesion group injected repeatedly with saline (lesion-saline group); and solid squares, NAc lesion group injected repeatedly with QNP (lesion-QNP group). The corresponding regression lines are as follows: thin solid line, sham-saline group; thin dashed line, lesion-saline group; thick solid line, sham-QNP group; and thick dashed line, lesion-QNP group.
Fig. 2
Fig. 2
Effects of chronic treatment with quinpirole (QNP) on the routes of travel in sham and nucleus accumbens core (NAc) lesion rats. Routes of travel are shown as path plots for a representative rat with a sham lesion (first and third rows) or NAc lesion (second and fourth rows) that was treated either with saline (top two rows) or QNP (bottom two rows). Locomotor trajectories during the entire 55 min session for injections one to 10 are shown. Each line represents a trajectory of locomotion and the density of trajectory lines corresponds to the amount of locomotion. Gray squares indicate locations of the four objects in the open field.
Fig. 3
Fig. 3
Effects of chronic treatment with quinpirole (QNP) on the distance traveled (a), 2 standard deviational ellipse (2SDE) (b), and path stereotypy (c) in sham and nucleus accumbens core (NAc) lesion rats. See Table 1 for parameters of the indicated regression lines. Open circles, sham-control group injected repeatedly with saline (sham-saline group); open squares, sham group injected repeatedly with QNP (sham-QNP group); solid circles, NAc lesion group injected repeatedly with saline (lesion-saline group); and solid squares, NAc lesion group injected repeatedly with QNP (lesion-QNP group). The corresponding regression lines are as follows: thin solid line, sham-saline group; thin dashed line, lesion-saline group; thick solid line, sham-QNP group; and thick dashed line, lesion-QNP group.

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