Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

UNLABELLED: Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. CONCLUSIONS: (a) These results confirm the importance of DA release in the NAc for reward-related states, with DA increasing in the core, but not shell subregion. (b) They provide first evidence that during the withholding of expected reward, DA decreases in the NAc core, but not shell region. (c) This decrease in DA appears only after a delay between delivery of reward and extinction likely due to it being masked by persisting DA release. We hypothesize the decrease in extinction-induced release of DA in the NAc core to be a marker for the despair/depression that is known to accompany the failure to obtain expected rewards/reinforcers.

Assessment of anxiolytic and panicolytic effects of dichloromethane fraction from stems of Kielmeyera coriacea.

Kielmeyera coriacea Mart. (Calophyllaceae) is known popularly as "Pau Santo". The hydroethanolic extract (HE) of Kielmeyera coriacea stems and its semi-pure dichloromethane (DCM) constituent produced an antidepressant-like effect in rats. The purpose of this study was to investigate the effects of repeated administration (21 days) by gavage of the DCM fraction (5, 10 or 15mg/kg) in rats submitted to the elevated T-maze (ETM), a model of generalized anxiety and panic disorders. The tricyclic antidepressant imipramine (15mg/kg) was used as a positive control. Rat locomotion was assessed using the open field test (OFT) following each drug treatment. The 2-hydroxy-1-methoxyxanthone (1), aucuparin (2), swertinin (3), 1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-xanthone (4) and 1,3,5-trihydroxy-2-(3-methylbut-2-enyl)-xanthone (5) were identified in DCM fraction, and suggest that the xanthone (4) is related with the antidepressant-like profile of this plant. Pharmacological evaluation showed that DCM fraction (10 and 15 mg/kg) decreased the inhibitory avoidance latency from the closed arm and increased the one-way escape latency from the open arm in the ETM, which is indicative of anxiolytic and panicolytic effects, respectively, as occurs with the positive control, imipramine (15 mg/kg), when compared to their control group (vehicle). Locomotor activity was not significantly altered by the different treatments. This study suggests that the DCM fraction from stems of Kielmeyera coriacea can be an important therapeutic alternative in the treatment of anxiety disorders, such as generalized anxiety and panic disorders.