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Early Cannabinoid Exposure as a Source of Vulnerability to Opiate Addiction: A Model in Laboratory Rodents

Published online by Cambridge University Press:  10 April 2014

Miguel Navarro*
Affiliation:
Complutense University of Madrid
Fernando Rodríguez de Fonseca
Affiliation:
Complutense University of Madrid
*
*Correspondence concerning this article should be addressed to Dr. Miguel Navarro, Departamento de Psicobiología. Facultad de Psicología.Universidad Complutense de Madrid. 28223 - Madrid (Spain). E-mail: [email protected]

Abstract

Recent findings have identified an endogenous brain system mediating the actions of cannabis sativa preparations. This system includes the brain cannabinoid receptor (CB-1) and its endogenous ligands anandamide and 2-arachidonoyl-glycerol. The endogenous cannabinoid system is not only present in the adult brain, but is also active at early stages of brain development. Studies developed at our laboratory have revealed that maternal exposure to psychoactive cannabinoid results in neuro-developmental alterations. A model is proposed in which early Δ9-tetrahydrocannabinol (THC) exposure during critical developmental periods results in permanent alterations in brain function by either the stimulation of CB-1 receptors present during the development, or by the alterations in maternal glucocorticoid secretion. Those alterations will be revealed in adulthood after challenges either with drugs (i.e. opiates) or with environmental stressors (i.e. novelty). They will include a modified pattern of neuro-chemical, endocrine, and behavioral responses that might lead ultimately to inadaptation and vulnerability to opiate abuse.

En los ultimos años se ha logrado identificar un sistema endógeno que media las acciones de los principios activos del cannabis sativa. Este sistema está compuesto por el receptor para cannabinoides cerebral (CB-1), y sus ligandos endógenos, la anandamida y el 2-araquidonilglicerol. El sistema cannabinoide endógeno está activo en el cerebro adulto, participando también en el desarrollo cerebral. Los estudios desarrollados en nuestro laboratorio han demostrado que la exposición maternal durante la gestación y la lactancia a compuestos activos en el receptor CB-1 conducen a alteraciones en el desarrollo cerebral. En este trabajo se propone un modelo en el cual la exposición durante periodos críticos del desarrollo a Δ9-tetrahydrocannabinol (THC), el principal cannabinoide psicoactivo del cannabis sativa, induce cambios permanentes en la función cerebral, bien mediante la activación de los receptores CB-1 presentes durante edades tempranas del desarrollo, o bien mediante la alteración de la secreción maternal de glucocorticoides. Estas alteraciones se manifiestan en la edad adulta tras la exposición a desafíos adaptativos, como el tratamiento con drogas de abuso (opiáceos) o el estrés medioambiental (novedad, etc.), que inducen respuestas neuroquímicas,hormonales y comportamentales anómalas, que se manifiestan como una mayor vulnerabilidad a la adicción.

Type
Spanish research trends
Copyright
Copyright © Cambridge University Press 1998

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