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Involvement of dopaminergic, opioidergic and CRH systems of long maternal separation effect on behavioral sensitization to stimulating effect of ethanol in male and female mice

Grant number: 07/01287-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2007
Effective date (End): July 31, 2011
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Deborah Suchecki
Grantee:Suzi Emiko Kawakami
Home Institution: Departamento de Psicobiologia. Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Behavioral sensitization to drugs of abuse is characterized by a progressive increase of locomotor activity after repeated administrations of the drugs and may have an important role on the development of drug dependence by increasing its motivational properties. Increased mesolimbic dopaminergic transmission is involved in the stimulant effects and in the behavioral sensitization process. Many studies show that dopaminergic receptor D1 is important for these effects. Numerous neurotransmitter and neuropeptide systems modulate the mesolimbic dopaminergic pathway, including the opioidergic and corticotrophin-releasing hormone (CRH) systems. It has been shown that nonspecific opioid antagonists have been used to treat ethanol dependence. Moreover, stress augments drug intake and behavioral responses to drugs of abuse and this effect may be due to the effects of the hypothalamic-pituitary-adrenal (HPA) axis components on the dopaminergic system. Several studies show that CRH antagonists may be an effective agent for treatment of ethanol dependence. Early life stress, such as long maternal separation during neonatal period, increases the vulnerability to drug abuse and this vulnerability may result from stress-induced alterations in the mesolimbic dopaminergic pathway and/or systems that act or modulate this pathway. The objectives of the present study were to verify the effects of long maternal separation on the basal and behavioral sensitization-induced dopamine concentrations in the mesolimbic pathway. Moreover, we intended to examine whether D1-, nonspecific opioid- (naltrexone) and CRH (alpha-helical CRH) antagonists could prevent the expression of behavioral sensitization in the early life-stressed animals.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
KAWAKAMI, SUZI E.; QUADROS, ISABEL M. H.; SUCHECKI, DEBORAH. Naltrexone Prevents in Males and Attenuates in Females the Expression of Behavioral Sensitization to Ethanol Regardless of Maternal Separation. FRONTIERS IN ENDOCRINOLOGY, v. 7, OCT 18 2016. Web of Science Citations: 2.
KAWAKAMI, S. E.; QUADROS, I. M. H.; MACHADO, R. B.; SUCHECKI, D. SEX-DEPENDENT EFFECTS OF MATERNAL SEPARATION ON PLASMA CORTICOSTERONE AND BRAIN MONOAMINES IN RESPONSE TO CHRONIC ETHANOL ADMINISTRATION. Neuroscience, v. 253, p. 55-66, DEC 3 2013. Web of Science Citations: 12.

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