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Updated: May 5, 2026
The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
Prenatal corticosterone and adolescent URB597 administration modulate emotionality and CB1 receptor expression in
Chiara Ceci1, Virginia Mela, Simone Macrì
1Section of Behavioral Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Rationale:
The central endocannabinoid system (eCB system) sustains the activity of the hypothalamus-pituitary-adrenal (HPA) axis in mediating individual emotional responses. Deviation in maturational trajectories of these two physiological systems, may persistently adjust individual behavioral phenotype.
Objective:
We investigated, in outbred CD1 male mice, whether exposure to prenatal stress may influence short- and long-term emotional and neurochemical responses to a pharmacological stimulation of the eCB system during adolescence.
Methods:
To mimic prenatal stress, pregnant mice were supplemented with corticosterone in the drinking water (33.3 mg/l); their adolescent male offspring received daily injections of the fatty acid amide hydrolase inhibitor, URB597 (0.4 mg/kg), in order to enhance eCB signaling. Mice were then tested for: locomotor activity during adolescence and locomotor activity, anxiogenic, and anhedonic profiles in adulthood. We analyzed the expression of CB1 receptors (CB1Rs) in prefrontal cortex, hippocampus, striatum, and cerebellum in adulthood.
Results:
Corticosterone administration (PC group) resulted, in adolescence, in a reduction in body weight and locomotion, while in adulthood, in increased anxiety-related behavior and reduced CB1Rs expression in cerebellum. URB597 exposure reduced locomotor activity and increased anhedonia in adulthood. CB1Rs were up-regulated in striatum and hippocampus and down-regulated in the cerebellum. PC-URB597 mice failed to show reductions in locomotion; exhibited increased risk assessment behavior; and showed reduced CB1Rs expression within the prefrontal cortex.
Conclusions:
Present results provide support to the hypothesis that precocious manipulations mapping onto the HPA axis and eCB system may persistently adjust individual emotional responses and eCB system plasticity.
