Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine

Female rats are intensely affected by cocaine, with estrogen probably playing an important role in this effect. Progesterone modulates the GABA system and attenuates the effects of cocaine; however, there is no information about its relevance in changing GABA synthesis pathways after cocaine adminis...

Full description

Bibliographic Details
Main Authors: M.F. Souza, V.M. Toniazo, A.P.G. Frazzon, H.M.T. Barros
Format: Article
Language:English
Published: Associação Brasileira de Divulgação Científica 2009-11-01
Series:Brazilian Journal of Medical and Biological Research
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2009001100011
_version_ 1818507266710568960
author M.F. Souza
V.M. Toniazo
A.P.G. Frazzon
H.M.T. Barros
author_facet M.F. Souza
V.M. Toniazo
A.P.G. Frazzon
H.M.T. Barros
author_sort M.F. Souza
collection DOAJ
description Female rats are intensely affected by cocaine, with estrogen probably playing an important role in this effect. Progesterone modulates the GABA system and attenuates the effects of cocaine; however, there is no information about its relevance in changing GABA synthesis pathways after cocaine administration to female rats. Our objective was to investigate the influence of progesterone on the effects of repeated cocaine administration on the isoenzymes of glutamic acid decarboxylase (GAD65 and GAD67) mRNA in brain areas involved in the addiction circuitry. Ovariectomized, intact and progesterone replacement-treated female rats received saline or cocaine (30 mg/kg, ip) acutely or repeatedly. GAD isoenzyme mRNA levels were determined in the dorsolateral striatum (dSTR) and prefrontal cortex (PFC) by RT-PCR, showing that repeated, but not acute, cocaine decreased GADs/&#946;-actin mRNA ratio in the dSTR irrespective of the hormonal condition (GAD65: P < 0.001; and GAD67: P = 0.004). In the PFC, repeated cocaine decreased GAD65 and increased GAD67 mRNA ratio (P < 0.05). Progesterone replacement decreased both GAD isoenzymes mRNA ratio after acute cocaine in the PFC (P < 0.001) and repeated cocaine treatment reversed this decrease (P < 0.001). These results suggest that cocaine does not immediately affect GAD mRNA expression, while repeated cocaine decreases both GAD65 and GAD67 mRNA in the dSTR of female rats, independently of their hormonal conditions. In the PFC, repeated cocaine increases the expression of GAD isoenzymes, which were decreased due to progesterone replacement.
first_indexed 2024-12-10T22:16:07Z
format Article
id doaj.art-fed59ca916524981b6bae25c36a41d43
institution Directory Open Access Journal
issn 0100-879X
1414-431X
language English
last_indexed 2024-12-10T22:16:07Z
publishDate 2009-11-01
publisher Associação Brasileira de Divulgação Científica
record_format Article
series Brazilian Journal of Medical and Biological Research
spelling doaj.art-fed59ca916524981b6bae25c36a41d432022-12-22T01:31:28ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2009-11-0142111068107510.1590/S0100-879X2009001100011Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaineM.F. SouzaV.M. ToniazoA.P.G. FrazzonH.M.T. BarrosFemale rats are intensely affected by cocaine, with estrogen probably playing an important role in this effect. Progesterone modulates the GABA system and attenuates the effects of cocaine; however, there is no information about its relevance in changing GABA synthesis pathways after cocaine administration to female rats. Our objective was to investigate the influence of progesterone on the effects of repeated cocaine administration on the isoenzymes of glutamic acid decarboxylase (GAD65 and GAD67) mRNA in brain areas involved in the addiction circuitry. Ovariectomized, intact and progesterone replacement-treated female rats received saline or cocaine (30 mg/kg, ip) acutely or repeatedly. GAD isoenzyme mRNA levels were determined in the dorsolateral striatum (dSTR) and prefrontal cortex (PFC) by RT-PCR, showing that repeated, but not acute, cocaine decreased GADs/&#946;-actin mRNA ratio in the dSTR irrespective of the hormonal condition (GAD65: P < 0.001; and GAD67: P = 0.004). In the PFC, repeated cocaine decreased GAD65 and increased GAD67 mRNA ratio (P < 0.05). Progesterone replacement decreased both GAD isoenzymes mRNA ratio after acute cocaine in the PFC (P < 0.001) and repeated cocaine treatment reversed this decrease (P < 0.001). These results suggest that cocaine does not immediately affect GAD mRNA expression, while repeated cocaine decreases both GAD65 and GAD67 mRNA in the dSTR of female rats, independently of their hormonal conditions. In the PFC, repeated cocaine increases the expression of GAD isoenzymes, which were decreased due to progesterone replacement.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2009001100011CocaineProgesteroneGAD mRNADorsolateral striatumPrefrontal cortex
spellingShingle M.F. Souza
V.M. Toniazo
A.P.G. Frazzon
H.M.T. Barros
Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine
Brazilian Journal of Medical and Biological Research
Cocaine
Progesterone
GAD mRNA
Dorsolateral striatum
Prefrontal cortex
title Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine
title_full Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine
title_fullStr Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine
title_full_unstemmed Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine
title_short Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine
title_sort influence of progesterone on gad65 and gad67 mrna expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine
topic Cocaine
Progesterone
GAD mRNA
Dorsolateral striatum
Prefrontal cortex
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2009001100011
work_keys_str_mv AT mfsouza influenceofprogesteroneongad65andgad67mrnaexpressioninthedorsolateralstriatumandprefrontalcortexoffemaleratsrepeatedlytreatedwithcocaine
AT vmtoniazo influenceofprogesteroneongad65andgad67mrnaexpressioninthedorsolateralstriatumandprefrontalcortexoffemaleratsrepeatedlytreatedwithcocaine
AT apgfrazzon influenceofprogesteroneongad65andgad67mrnaexpressioninthedorsolateralstriatumandprefrontalcortexoffemaleratsrepeatedlytreatedwithcocaine
AT hmtbarros influenceofprogesteroneongad65andgad67mrnaexpressioninthedorsolateralstriatumandprefrontalcortexoffemaleratsrepeatedlytreatedwithcocaine