Abstract
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.
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Acknowledgments
This research was supported by “ECB-EMOTION: resilience” from the Dep. of Antidrug Policies c/o Presidency of the Council of Ministres (Italy) to GL and SM and from Instituto de Salud Carlos III (Spain), Redes temáticas de Investigación Cooperativa en salud RD06/0001/1013; GRUPOS UCM-BSCH (GRUPO UCM 951579) to EMM and MPV.
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Ceci, C., Mela, V., Macrì, S. et al. Prenatal corticosterone and adolescent URB597 administration modulate emotionality and CB1 receptor expression in mice. Psychopharmacology 231, 2131–2144 (2014). https://doi.org/10.1007/s00213-013-3367-3
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DOI: https://doi.org/10.1007/s00213-013-3367-3