Effects of prenatal and postnatal maternal ethanol on offspring response to alcohol and psychostimulants in long evans rats.
An important factor that may influence addiction liability is exposure during the early life period. Exposure to ethanol, early in life, can have long-lasting implications on brain function and drugs of abuse response later in life. In the present study we investigated the behavioral responses to ethanol and to psychostimulants in Long Evans rats that have been exposed to pre- and postnatal ethanol. Since a relationship between heightened drug intake and susceptibility to drug-induced locomotor activity/sensitization has been demonstrated, we tested these behavioral responses, in control and early life ethanol-exposed animals. The young adult male and female progeny were tested for locomotor response to alcohol, cocaine and d-amphetamine. Sedative, rewarding effects of alcohol and alcohol consumption were measured. Our results show that early life ethanol exposure behaviorally sensitized animals to subsequent ethanol and psychostimulants exposure. Ethanol-exposed animals were also more sensitive to the hyperlocomotor effects of all drugs of abuse tested and to those of the dopamine receptor agonist apomorphine. Locomotor sensitization to repeated injections of cocaine was facilitated in ethanol-exposed animals. Ethanol-induced conditioned place preference was also facilitated in ethanol-exposed animals. Ethanol consumption and preference were increased after early life ethanol exposure and this was associated with decreased sensitivity to the sedative effects of ethanol. The altered behavioral responses to drugs of abuse were associated with decreased striatal dopamine transporter and hippocampal NMDAR binding. Our results outline an increased vulnerability to rewarding and stimulant effects of ethanol and psychostimulants and support the epidemiological and clinical data that suggested that early chronic exposure to ethanol may increase the propensity for later self-administration of ethanol or other substances.
Equipe région INSERM 24 (ERI24), Groupe de Recherche sur l'alcool et les Pharmacodépendances, Université de Picardie Jules Verne, Faculté de pharmacie, 1 rue des Louvels, 80000 Amiens, France.
E
E
Barbier
H
H
Houchi
V
V
Warnault
O
O
Pierrefiche
M
M
Daoust
M
M
Naassila
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D008098:Litter Size / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012021:Reflex, Abnormal
D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol