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Homeostatic role of the endocannabinoid system and consequences of its disregulation on emotional states

Maria-Paz Viveros1*
  • 1 Facultad de Biologia, Universidad Complutense de Madrid, Departamento de Fisiologia (Fisiologia Animal II), Spain

The endocannabinoid system (ECS) plays a crucial role in brain development, emotional homeostasis and motivational status. Our studies are focussed on these aspects during critical developmental periods. We have analyzed short and long-term psychophysiological consequences of adolescent exposure to cannabinoids as well as its interactions with a model of neonatal stress, maternal deprivation, and with other drugs of abuse. We have carried out multidisciplinary analyses from molecular indices of brain plasticity to different aspects of cognitive function as well as stress and anxiety responses in different behavioral tests. The results of these studies, with an special emphasis in the ECS, are particularly relevant within the context of emotional responses and motivations linked to polydrug abuse and the impact of early life stressful events as factors of vulnerability for the development of neuropsychiatric disorders. As for our work on adolescence animal models, we have shown sex-dependent effects of acute and chronic cannabinoid administration on anxiety related behaviour, cognitive function and metabolic parameters as well as sex-dependent functional interactions of cannabinoids with nicotine and MDMA (“ecstasy”), among other drugs. We have revealed that a single prolonged episode of maternal deprivation (24 hours at PND 9) induces short and long- term sex-dependent psychoneuroendocrine effects, including alterations in the developing brain affecting neurons, glia, major synaptic plasticity players, CB1 and CB2 cannabinoid receptors and endocannabinoid levels. On the basis of our results we propose that this model provides a useful tool to further address the neurodevelopmental theory proposed for certain psychiatric disorders, as many of the developmental alterations found in these animals might well be related to their altered behaviour later in life. In addition, this animal model may contribute to clarify the involvement of the ECS in brain development and the consequences of its dis-regulation in early developmental periods. Our work highlights the importance of analysing sexual dimorphisms in experimental studies involving not only adult but also immature animals. This strategy may shed light on a possible neurodevelopmental basis for sex differences observed in several psychiatric diseases, as well as on the possibly influence of sex on the modulatory role of the endocannabinoid system throughout neurodevelopment. Finally, our studies about the consequences of cannabinoids administration on anxiety responses have contributed to explain the mechanisms underlying the observed biphasic effects. In particular, to clarify the role of CB1 receptor in this biphasic effect, we used two different conditional CB1 receptor knockout (KO) mouse lines, GABA-CB1-KO (CB1 receptor inactivation in forebrain GABAergic neurons) and Glu-CB1-KO (CB1 receptor inactivation in cortical glutamatergic neurons).

Acknowledgements

SAF2006-07523; BFU2009-10109, Redes temáticas de Investigación Cooperativa en salud (ISCIII y FEDER): RD06/0001/1013; GRUPOS UCM-BSCH (951579) and Plan Nacional sobre Drogas (SAS/125/2009)

References

Marco, E.M., Viveros, M.P. (2009). The critical role of the endocannabinoid system in emotional homeostasis: avoiding excess and deficiencies. Mini Rev. Med. Chem. 9, 1407-15.

Mateos, B., Borcel, E., Loriga, R., Luesu, W., Bini, V., Llorente, R., Castelli, M., Viveros, M.P. Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB1 cannabinoid receptors (2011). J Psychopharmacol. 25, 1676-90

Rey, A.A., Purrio, M-, Viveros, M.P., Lutz, B. Biphasic effects of cannabinoids in anxiety responses: CB1 and GABA(B) receptors in the balance of GABAergic and glutamatergic neurotransmission (2012). Neuropsychopharmacology 37, 2624-34.

Suárez, J., Rivera, P., Llorente, R., Romero-Zerbo, S.Y., Bermúdez-Silva, F.J., de Fonseca, F.R., Viveros, M.P. (2010). Early maternal deprivation induces changes on the expression of 2-AG biosynthesis and degradation enzymes in neonatal rat hippocampus. Brain Res. 1349, 162-73.

Viveros, M.P., Llorente, R., Suarez, J., Llorente-Berzal, A., López-Gallardo, M., de Fonseca, F.R. (2012) The endocannabinoid system in critical neurodevelopmental periods: sex differences and neuropsychiatric implications. J Psychopharmacol. 26,164-76.

Viveros, M.P., Marco, E.M., File, S.E. (2005) Endocannabinoid system and stress and anxiety responses. Pharmacol. Biochem. Behav. 81, 331-42.

Keywords: Cannabinoid system, adolescence, Maternal Deprivation, drugs of abuse, Animal Models, sex differences, polydrug use, Anxiety, cognition-emotion, synaptic plasticity, conditional CB1 knockout mice

Conference: 4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.

Presentation Type: Symposium

Topic: Abstracts

Citation: Viveros M (2013). Homeostatic role of the endocannabinoid system and consequences of its disregulation on emotional states. Conference Abstract: 4th Conference of the Mediterrarnean Neuroscience Society. doi: 10.3389/conf.fnhum.2013.210.00070

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Received: 25 Jan 2013; Published Online: 11 Apr 2013.

* Correspondence: Prof. Maria-Paz Viveros, Facultad de Biologia, Universidad Complutense de Madrid, Departamento de Fisiologia (Fisiologia Animal II), Madrid, Madrid, 28040, Spain, pazviver@bio.ucm.es