Acute Fasting Produces Antidepressant-Like Effects Via Down Regulation Of5-TH₂Receptors And Enhancement Of CREB Phosphorylation.

Depression is a common neural illness associated with high rates of chronicity, recurrence, andpsychosocial impairments. Depressive state is associated with alterations in synapticneurotransmitter concentration or neurotransmitter receptor sensitivity, such as upregulation of5-hydroxytryptarnine2（5-HT₂） receptor activity. The need for the discovery of alternative orcomplementary antidepressants and to elucidate their mechanism of action is evident.Intermittent fasting and caloric restriction have been linked to longevity, mood improvement andsometimes euphoria in all animal species in which they have been tested. However, there is noliterature demonstrating antidepressant-like effect of acute fasting and corresponding mechanismof action. The present research sought to investigate the antidepressant-like effect of acutefasting in the forced swimming test （FST）. The research further aimed to investigate the effectsof fasting on the levels of the transcription factor cAMP response element-binding protein（CREB） and its phosphorylated form （p-CREB） as well as the neurotrophin, brain derivednuerotrophic factor （BDNF） in the frontal cortex and hippocampus:-brain regions implicated inthe pathophysiology of depression.9, but not3or18hours, of fasting significantly reducedimmobility time in FST without accompanying changes in locomotor activity when assessed inan open field test （OFT）. Western blot analysis also revealed that9hours of fasting enhancedphosphorylation of CREB, as molecular mechanism for the antidepressant-like effects, thoughELISA analysis of BDNF did not show significant difference. Co-administration of a classicantidepressant, Imipramine （30mg/kg, i.p）, and9hour fasting produced an additive effect both inFST and phosphorylation of CREB. The additive effect was reversed by treatment with apreferential5-HT₂Areceptor agonist,（±）-1-（2,5-dimethoxy-4-iodophenyl）-2-aminopropanehydrochloride （DOI）（5mg/kg, s.c） prior to FST and CREB analysis, suggesting involvement of5-HT₂receptors in the mechanism of action. Taken together, the present research showed thatfasting produces antidepressant-like effects in FST, at least in part, via down regulation of5-HT₂receptors and enhancement of CREB phosphorylation. Furthermore, fasting has additive effectswith Imipramine.