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


OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Schneider
Tomasz
T
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Ziòłkowska
Barbara
B
Gieryk
Agnieszka
A
Tyminska
Anna
A
Przewłocki
Ryszard
R
D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D001007:Anxiety / Q000139:chemically induced; D001321:Autistic Disorder / Q000139:chemically induced*; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004644:Emotions / Q000187:drug effects; D004745:Enkephalins / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007858:Learning / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011498:Protein Precursors / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D014635:Valproic Acid / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D004298:Dopamine