Name: Martielo Januário da Mata
Type: MSc dissertation
Publication date: 16/09/2016

Namesort descending Role
Ana Paula Santana de Vasconcellos Bittencourt Advisor *

Examining board:

Namesort descending Role
Ana Paula Santana de Vasconcellos Bittencourt Advisor *
Carla Dalmaz External Examiner *
Rita Gomes Wanderley Pires Internal Examiner *
Vanessa Beijamini Harres Internal Alternate *

Summary: Maternal separation is an animal model used to mimic stressful events in the neonatal period, which may lead to the development of cognitive impairments and substances abuse, such as ethanol. This substance is a potential risk to health due to its high consumption by young people, and its consumption alters behavior and neurotransmitter systems function, such as dopaminergic and endocannabinoid systems. In this study, we evaluate the influence of ethanol binge drinking in adolescent rats subjected to maternal separation on learning, impulsivity and voluntary ethanol consumption in adulthood, as well as (the effects of these treatments) on the endocannabinoid and dopaminergic systems. For this, male Wistar rats were separated from their mothers or not (control group) during the postnatal days (DPN) 2-15, for 3 hours daily. Animals not separated were kept on animal facility reared conditions. At DPN 35, the animals were divided in acute or chronic treatment. Both groups were again divided into 3 subgroups, which receive vehicle (saline) or ethanol in doses of 3.0 or 6.0 g/kg by intragastric administration. Ethanol was administered during three consecutive days (acute treatment) or once a day, two consecutive days, interspersed by two days without ethanol, totalizing 10 doses (chronic treatment). At the end of this procedure, the animals were subjected to behavioral tests (learning and impulsivity tests), both using a T-maze, and to the voluntary ethanol consumption test, or euthanized for prefrontal cortex and hippocampus removal. The mRNA expression of the components of the endocannabinoid system: CB1, monoacylglycerol lipase, fatty acid amide hydrolase, N-acyl-phosphatidylethanolamine phospholipase D and diacylglycerol lipase were evaluated in both structures, and the dopaminergic receptors D1, D2 and tyrosine hydroxylase enzyme were evaluated only in the prefrontal cortex. We observed that maternal separation increased impulsivity behavior and voluntary consumption of ethanol, and ethanol in adolescence impaired short-term memory and appears to reverse other behavioral changes due to maternal separation. In the prefrontal cortex, maternal separation and ethanol altered dopaminergic system with reduction of D1 mRNA expression and increased tyrosine hydroxylase, and appears to increase the enzymes for endocannabinoid synthesis, N-acyl-phosphatidylethanolamine phospholipase D e diacylglycerol lipase. In the hippocampus, the group submitted to both treatments presented a reduction of CB1 mRNA expression and the enzyme N-acyl-phosphatidylethanolamine phospholipase D, and an increased expression of diacylglycerol lipase. In conclusion, maternal separation and ethanol were able to cause behavioral changes and modifications in endocannabinoid and dopaminergic systems, and maternal separation modifies ethanol effects response.

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