Differential behavioral profile induced by the injection of dipotassium chlorazepate within brain areas that project to the nucleus accumbens septi

AbstractBackground:In previous studies, we have observed that specificN-methyl-d-aspartic acid (NMDA) antagonists and non-NMDA antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the plus maze test in rats. In the present study, the effect of intracanalicular blockade of NMDA receptors using dizocilpine in the plus maze was studied in male rats bilaterally cannulated NAS.Methods:Rats were divided into five groups that received either 1 μL injections of saline or dizocilpine (MK-801, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine) in different doses (0.5, 1, 2, or 4 μg) 15 min before testing.Results:Time spent in the open arm increased under dizocilpine treatment with the two higher doses (2 and 4 μg, p<0.05), extreme arrivals were increased by the three higher doses (1 μg, p<0.05; 2 and 4 μg, p<0.01), and open arm entries by the three higher doses (1, 2, and 4 μg, p<0.05). A dose-effect relationship was observed in all cases.Conclusions:We conclude that dizocilpine-glutamatergic blockade in the accumbens lead to an anxiolytic-like effect and a behavioral disinhibition related to an increase in some motoric parameters, showing specific behavioral patterns.

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Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder

Neuropsychopharmacology ◽

10.1038/s41386-020-0686-z ◽

2020 ◽

Vol 45 (11) ◽

pp. 1931-1941 ◽

Cited By ~ 5

Author(s):

Adele Romano ◽

Maria Vittoria Micioni Di Bonaventura ◽

Cristina Anna Gallelli ◽

Justyna Barbara Koczwara ◽

Dorien Smeets ◽

...

Keyword(s):

Eating Disorder ◽

Nucleus Accumbens ◽

Food Intake ◽

Binge Eating ◽

Binge Eating Disorder ◽

Female Rats ◽

Early Gene ◽

Mrna Levels ◽

Palatable Food ◽

Brain Areas

Abstract Binge eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell (“frustration stress”). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg−1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior.

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