Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.
Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring.
Barbier
Estelle
E
Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l'Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, 1 rue des Louvels, 80000 Amiens, France.
Pierrefiche
Olivier
O
Vaudry
David
D
Vaudry
Hubert
H
Daoust
Martine
M
Naassila
Mickaël
M
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000235:genetics; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019966:Substance-Related Disorders / Q000523:psychology*
D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; C546281:Gabrg2 protein, rat; C473649:NR1A NMDA receptor, rat; D043884:Receptor, Cannabinoid, CB1; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D000661:Amphetamine; D003042:Cocaine