Adolescent intermittent ethanol exposure does not alter responsiveness to ifenprodil or expression of vesicular GABA and glutamate transporters

Abstract Aim Reinforcing properties of ethanol and cocaine are mediated in part through the glutamatergic system. Extracellular glutamate concentration is strictly maintained through several glutamate transporters, such as glutamate transporter 1 (GLT-1), cystine/glutamate transporter (xCT) and glutamate aspartate transporter (GLAST). Previous findings revealed that cocaine and ethanol exposure downregulated GLT-1 and xCT, and that β-lactam antibiotics restored their expression. Methods In this study, we investigated the effect of ampicillin/sulbactam (AMP/SUL) (200 mg/kg, i.p.), a β-lactam antibiotic, on cocaine-induced reinstatement and locomotor activity in male alcohol preferring (P) rats using free choice ethanol (15 and 30%, v/v) and water. We also investigated the effect of co-exposure to ethanol and cocaine (20 mg/kg, i.p.) on GLT-1, xCT and GLAST expression in the nucleus accumbens (NAc) core, NAc shell and dorsomedial prefrontal cortex (dmPFC). Results Cocaine exposure decreased ethanol intake and preference. Cocaine and ethanol co-exposure acquired place preference and increased locomotor activity compared to ethanol-exposed rats. GLT-1 and xCT expression were downregulated after cocaine and ethanol co-exposure in the NAc core and shell, but not in dmPFC. AMP/SUL attenuated reinstatement to cocaine as well attenuated the decrease in locomotor activity and ethanol intake and preference. These effects were associated with upregulation of GLT-1 and xCT expression in the NAc core/shell and dmPFC. GLAST expression was not affected after ethanol and cocaine co-exposure or AMP/SUL treatment. Conclusion Our findings demonstrate that astrocytic glutamate transporters within the mesocorticolimbic area are critical targets in modulating cocaine-seeking behavior while being consuming ethanol.

Download Full-text

DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early life stress and ethanol exposure in adulthood

10.21203/rs.3.rs-279273/v1 ◽

2021 ◽

Author(s):

Maria Vrettou ◽

Liying Yan ◽

Kent Nilsson ◽

Åsa Wallén-Mackenzie ◽

Ingrid Nylander ◽

...

Keyword(s):

Dna Methylation ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Glutamate Transporters ◽

Ethanol Consumption ◽

Ethanol Exposure ◽

Ethanol Drinking ◽

Vesicular Glutamate Transporters

Abstract DNA methylation and gene expression can be altered by early life stress (ELS) and/or ethanol consumption. The present study aimed to investigate whether DNA methylation of the Vesicular Glutamate Transporters (Vglut)1–3 is related to previously observed Vglut1-3 transcriptional differences in the ventral tegmental area (VTA), nucleus accumbens (Acb), dorsal striatum (dStr) and medial prefrontal cortex (mPFC) of adult rats exposed to ELS, modelled by maternal separation, and voluntary ethanol consumption. Targeted next-generation bisulfite sequencing was performed to identify the methylation levels on 61 5′-cytosine-phosphate-guanosine-3′ sites (CpGs) in potential regulatory regions of Vglut1, 53 for Vglut2, and 51 for Vglut3. In the VTA, ELS in ethanol-drinking rats was associated with Vglut1-2 CpG-specific hypomethylation, whereas bidirectional Vglut2 methylation differences at single CpGs were associated with ELS alone. Exposure to both ELS and ethanol, in the Acb, was associated with lower promoter and higher intronic Vglut3 methylation; and in the dStr, with higher and lower methylation in 26% and 43% of the analyzed Vglut1 CpGs, respectively. In the mPFC, lower Vglut2 methylation was observed upon ELS- or ethanol-only. The present findings suggest Vglut1-3 CpG-specific methylation signatures of ELS and ethanol drinking, underlying previously reported Vglut1-3 transcriptional differences in the mesocorticolimbic brain.

Download Full-text

DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early-life stress and adult ethanol exposure—an explorative study

Scientific Reports ◽

10.1038/s41598-021-94739-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maria Vrettou ◽

Liying Yan ◽

Kent W. Nilsson ◽

Åsa Wallén-Mackenzie ◽

Ingrid Nylander ◽

...

Keyword(s):

Dna Methylation ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Glutamate Transporters ◽

Ethanol Consumption ◽

Ethanol Exposure ◽

Ethanol Drinking ◽

Vesicular Glutamate Transporters

AbstractDNA methylation and gene expression can be altered by early life stress (ELS) and/or ethanol consumption. The present study aimed to investigate whether DNA methylation of the Vesicular Glutamate Transporters (Vglut)1-3 is related to previously observed Vglut1-3 transcriptional differences in the ventral tegmental area (VTA), nucleus accumbens (Acb), dorsal striatum (dStr) and medial prefrontal cortex (mPFC) of adult rats exposed to ELS, modelled by maternal separation, and voluntary ethanol consumption. Targeted next-generation bisulfite sequencing was performed to identify the methylation levels on 61 5′-cytosine-phosphate-guanosine-3′ sites (CpGs) in potential regulatory regions of Vglut1, 53 for Vglut2, and 51 for Vglut3. In the VTA, ELS in ethanol-drinking rats was associated with Vglut1-2 CpG-specific hypomethylation, whereas bidirectional Vglut2 methylation differences at single CpGs were associated with ELS alone. Exposure to both ELS and ethanol, in the Acb, was associated with lower promoter and higher intronic Vglut3 methylation; and in the dStr, with higher and lower methylation in 26% and 43% of the analyzed Vglut1 CpGs, respectively. In the mPFC, lower Vglut2 methylation was observed upon exposure to ELS or ethanol. The present findings suggest Vglut1-3 CpG-specific methylation signatures of ELS and ethanol drinking, underlying previously reported Vglut1-3 transcriptional differences in the mesocorticolimbic brain.

Download Full-text

Reversal of cardiomyopathy resulting from prenatal exposure to ethanol

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100113469 ◽

1984 ◽

Vol 42 ◽

pp. 716-717

Author(s):

C. Uphoff ◽

C. Nyquist-Battie

Keyword(s):

Prenatal Exposure ◽

Heart Development ◽

Membrane Integrity ◽

Ethanol Exposure ◽

Prenatal Ethanol Exposure ◽

Pathological Changes ◽

Prenatally Exposed ◽

Inner Mitochondrial Membrane ◽

Fetal Alcohol ◽

Newborn Mice

Fetal Alcohol Syndrone (FAS) is a syndrome with characteristic abnormalities resulting from prenatal exposure to ethanol. In many children with FAS syndrome gross pathological changes in the heart are seen with septal defects the most prevalent abnormality recorded. Few studies in animal models have been performed on the effects of ethanol on heart development. In our laboratory, it has been observed that prenatal ethanol exposure of Swiss albino mice results in abnormal cardiac muscle ultrastructure when mice were examined at birth and compared to pairfed and normal controls. Fig. 1 is an example of the changes that are seen in the ethanol-exposed animals. These changes include enlarged mitochondria with loss of inner mitochondrial membrane integrity and loss of myofibrils. Morphometric analysis substantiated the presence of these alterations from normal cardiac ultrastructure. The present work was undertaken to determine if the pathological changes seen in the newborn mice prenatally exposed to ethanol could be reversed with age and abstinence.

Download Full-text

Alterations in Ultrastructure of Skeletal Muscle From Newborn Guinea Pigs Following in Utero Exposure to Ethanol

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120126 ◽

1985 ◽

Vol 43 ◽

pp. 686-687

Author(s):

C. Uphoff ◽

C. Nyquist-Battie ◽

T.B. Cole

Keyword(s):

Skeletal Muscle ◽

Guinea Pigs ◽

Muscle Development ◽

In Utero ◽

Ethanol Exposure ◽

Prenatally Exposed ◽

Chronic Alcoholic ◽

Test Kit ◽

Food And Water Intake ◽

Post Intubation

Ultrastructural alterations of skeletal muscle have been observed in adult chronic alcoholic patients. However, no such study has been performed on individuals prenatally exposed to ethanol. In order to determine if ethanol exposure in utero in the latter stages of muscle development was deleterious, skeletal muscle was obtained from newborn guinea pigs treated in the following manner. Six Hartly strain pregnant guinea pigs were randomly assigned to either the ethanol or the pair-intubated groups. Twice daily the 3 ethanol-treated animals were intubated with Ensure (Ross Laboratories) liquid diet containing 30% ethanol (6g/Kg pre-pregnant body weight per day) from day 35 of gestation until parturition at day 70±1 day. Serum ethanol levels were determined at 1 hour post-intubation by the Sigma alcohol test kit. For pair-intubation the Ensure diet contained sucrose substituted isocalorically for ethanol. Both food and water intake were monitored.

Download Full-text