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1.
Article in English | MEDLINE | ID: mdl-38565388

ABSTRACT

While there is extensive research on alcohol dependence, the factors that make an individual vulnerable to developing alcoholism haven't been explored much. In this study, we aim to investigate how neonatal exposure to sex hormones affects alcohol intake and the regulation of the mesolimbic pathway in adulthood. The study aimed to investigate the impact of neonatal exposure to a single dose of testosterone propionate (TP) or estradiol valerate (EV) on ethanol consumption in adult rats. The rats were subjected to a two-bottle free-choice paradigm, and the content of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens (NAcc) was measured using HPLC-ED. The expression of critical DA-related proteins in the mesolimbic pathway was evaluated through RT-qPCR and western blot analysis. Supraphysiological neonatal exposure to EV or TP resulted in increased ethanol intake over four weeks in adulthood. In addition, the DA and DOPAC content was reduced and increased in the NAcc of EV and TP-treated rats, and ß-endorphin content in the hypothalamus decreased in EV-treated rats. The VTA µ receptor and DA type 2 form short receptor (D2S) expression were significantly reduced in EV and TP male rats. Finally, in an extended 6-week protocol, the increase in ethanol consumption induced by EV was mitigated during the initial two hours post-naloxone injection. Neonatal exposure to sex hormones is a detrimental stimulus for the brain, which can facilitate the development of addictive behaviors, including alcohol use disorder.


Subject(s)
3,4-Dihydroxyphenylacetic Acid , Alcohol Drinking , Animals, Newborn , Dopamine , Estradiol , Nucleus Accumbens , Testosterone Propionate , Animals , Male , Alcohol Drinking/metabolism , Rats , Nucleus Accumbens/metabolism , Nucleus Accumbens/drug effects , Estradiol/pharmacology , Testosterone Propionate/pharmacology , Testosterone Propionate/administration & dosage , Dopamine/metabolism , 3,4-Dihydroxyphenylacetic Acid/metabolism , Female , Ethanol/pharmacology , Ethanol/administration & dosage , Gonadal Steroid Hormones/metabolism , Rats, Sprague-Dawley
2.
Dev Psychobiol ; 62(4): 519-531, 2020 05.
Article in English | MEDLINE | ID: mdl-31564064

ABSTRACT

Repeated exposure to alcohol increases retrieval of fear-conditioned memories, which facilitates, among other factors, the emergence of post-traumatic stress disorder (PTSD). Individuals with PTSD are more likely to develop alcohol and substance abuse related disorders. We assessed if prenatal and early postnatal alcohol exposure (PAE) increased the susceptibility to retain aversive memories and if this was associated with subsequent heightened alcohol consumption. Pregnant Sprague-Dawley rats were exposed for 22 hr/day, throughout pregnancy and until postnatal Day 7 to a single bottle of sucralose - sweetened 10% alcohol solution (PAE Group), or to a single bottle of tap water and sucralose (Control Group). Auditory fear conditioning (AFC) was performed in the adolescent offspring at postnatal Day 40. Freezing was measured during acquisition, retention and extinction phases, followed by 3 weeks of free choice alcohol intake. Female, but not male, PAE rats exhibited impaired extinction of the aversive memory, a finding associated with higher levels of 3-4 Dihidroxyphenylacetic acid (DOPAC) in the nucleus accumbens and heightened alcohol intake, respect to controls. These findings suggest that PAE makes females more vulnerable to long-term retention of aversive memories, which coexist with heightened alcohol intake. These findings are reminiscent of those of PTSD.


Subject(s)
Alcohol Drinking/physiopathology , Alcoholism/physiopathology , Behavior, Animal/drug effects , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Extinction, Psychological/drug effects , Fear/physiology , Prenatal Exposure Delayed Effects/physiopathology , Stress Disorders, Post-Traumatic/physiopathology , Age Factors , Animals , Auditory Perception/physiology , Central Nervous System Depressants/administration & dosage , Conditioning, Psychological/physiology , Disease Models, Animal , Ethanol/administration & dosage , Female , Fetal Alcohol Spectrum Disorders/physiopathology , Male , Pregnancy , Rats , Rats, Sprague-Dawley , Sex Factors
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