Prenatal exposure to valproic acid disturbs the enkephalinergic system functioning, basal hedonic tone, and emotional responses in an animal model of autism

• Published in: Psychopharmacologia 2007-09, Vol.193 (4), p.547-555
• Main Authors: SCHNEIDER, Tomasz, ZIOLKOWSKA, Barbara, GIERYK, Agnieszka, TYMINSKA, Anna, PRZEWŁOCKI, Ryszard
• Format: Article
• Language: English
• Subjects: Amygdala; Animal models; Animals; Anticonvulsants - toxicity; Anxiety; Anxiety - chemically induced; Autism; Autistic Disorder - chemically induced; Aversion; Basal Ganglia - drug effects; Basal Ganglia - metabolism; Biological and medical sciences; Brain; Caudate-putamen; Child clinical studies; Conditioning, Classical - drug effects; Developmental disorders; Disease Models, Animal; Dopamine - metabolism; Dopamine receptors; Embryos; Emotions; Emotions - drug effects; Enkephalins - drug effects; Enkephalins - metabolism; Female; gamma-Aminobutyric Acid - metabolism; Gene Expression; Hedonic response; Human exposure; Hybridization; Infantile autism; Learning; Learning - drug effects; Male; Maze Learning - drug effects; Medical sciences; Memory - drug effects; Mesolimbic system; Naloxone; Narcotics; Neostriatum; Neurology; Nucleus accumbens; Opioid peptides; Opioids; Pattern recognition; Pharmacology; Pregnancy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects; Proenkephalin; Protein Precursors - drug effects; Protein Precursors - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Wistar; Recognition, Psychology - drug effects; RNA, Messenger - metabolism; Valproic acid; Valproic Acid - toxicity; γ-Aminobutyric acid
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-007-0795-y

It has been suggested that behavioral aberrations observed in autism could be the result of dysfunction of the neuroregulatory role performed by the endogenous opioid peptides. Many of those aberrations have been recently modeled in rats exposed to valproic acid (VPA) on the 12th day of gestation (VPA rats). The aim of the present study was to elucidate functioning of the enkephalinergic system, one of the endogenous opioid peptide systems strongly involved in emotional responses, in VPA rats using both biochemical and behavioral methods. In situ hybridization was used to measure proenkephalin mRNA expression in adult VPA rats' central nucleus of the amygdala, the dorsal striatum, and the nucleus accumbens. Additional groups of animals were examined in a conditioned place aversion to naloxone, the elevated plus maze, and object recognition tests to assess their basal hedonic tone, anxiety, learning and memory, respectively. Prenatal exposure to VPA decreased proenkephalin mRNA expression in the dorsal striatum and the nucleus accumbens but not in the central nucleus of the amygdala. It also increased anxiety and attenuated conditioned place aversion to naloxone but had no impact on learning and memory. The present results suggest that prenatal exposure to VPA may lead to the decreased activity of the striatal enkephalinergic system and in consequence to increased anxiety and disregulated basal hedonic tone observed in VPA rats. Presented results are discussed in light of interactions between enkephalinergic, GABAergic, and dopaminergic systems in the striatum and mesolimbic areas of the brain.