Effect of long-term caffeine administration on depressive-like behavior in rats exposed to chronic unpredictable stress

Abstract

Chronic unpredictable stress (CUS) was used to study the effects of a long-term treatment with either caffeine (8 mg/kg, orally) or desipramine (DMI) (10 mg/kg, intraperitoneally) in Wistar rats. The CUS procedure was applied for 6 weeks. Animals underwent a 2-week drug-free CUS procedure. Drugs were administered for 4 weeks alongside the stress and both drug and stress were continued throughout the behavioral testing period. CUS-exposed rats showed depressive-like behavior with reduced weight gain, reduced consumption of sucrose solution, increased immobility in the forced swimming test, and hypolocomotion in an open field. For the open field and elevated plus maze, calculation of an anxiety index confirmed that CUS increased anxiety, which was accompanied by an increase in the core temperature. DMI counteracted these physical and behavioral changes. Caffeine caused similar effects to DMI on weight gain, motor activity, anxiety level, and core temperature. In CUS-exposed rats, caffeine showed antidepressant and anxiolytic activity, accompanied by increased hippocampal dopamine and serotonin levels. However, no significant change in weight gain or core temperature was observed after caffeine treatment in CUS-exposed rats. These results suggest that, similar to the antidepressant DMI, long-term caffeine exposure exerts an antidepressant and anxiolytic effect in the CUS model. The involvement of the dopaminergic and serotonergic systems is discussed.

Antidepressant-like effects of paeoniflorin on the behavioural, biochemical, and neurochemical patterns of rats exposed to chronic unpredictable stress

“…It is considered as the most valuable and stable model of depression in animals [7]. The results of the present study showed that rats subjected to a 7-week period of CUS exhibited depressive-like behaviour with reduced weight, low motor activity, increased defecation and reduced consumption of sucrose compared with the control group, in consistency with many previous reports [2,22,23]. The sucrose preference test is an indicator of anhedonia-like behavioural change [27].…”

Caffeine acts through neuronal adenosine A 2A receptors to prevent mood and memory dysfunction triggered by chronic stress

“…The prevention of different alterations caused by repeated stress by regular (not acute) caffeine consumption had been noted previously by others (36)(37)(38) and is in tight agreement with the inverse correlation between caffeine intake and the incidence of depression (5,6). Given that caffeine intake increases in stressed individuals (4), it is tempting to speculate that this increased intake may be a prophylactic antistress measure to normalize mood-related behavioral changes by normalizing synaptic functions via A 2A R blockade.…”

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

“…Orally administered inosine also reproduces this effect (Muto et al, 2014). Interestingly A 2A receptor gene deficiency and A 2A receptor antagonists, including caffeine, also have antidepressant-like effect in the FST and TST (El Yacoubi et al, 2003;Hodgson et al, 2009) as well as in the chronic unpredictable stress paradigm of depression (Pechlivanova et al, 2012).…”