Long-term social isolation and medial prefrontal cortex: dopaminergic and cholinergic neurotransmission.
Rearing rats in social isolation has been suggested as an animal model of schizophrenia, based mainly on the similarity between the attenuation of prepulse inhibition (PPI) in isolated rats and in schizophrenic patients. The medial prefrontal cortex (mPFC) plays a major role in the pathophysiology of schizophrenia. Thus, a postmortem micropunch analysis measuring dopamine (DA), DOPAC (3,4-dihydroxyphenylacetic acid) and homovanillic acid (HVA) in the dorsal and ventral subregion of the mPFC, the caudate putamen (CPu) and nucleus accumbens (NAc) was carried out on socially isolated or group-housed male Sprague-Dawley (SD) rats. Additionally, in vivo microdialysis with D-amphetamine (1 mg/kg ip) stimulation was performed in isolated animals and their controls, examining the ventral mPFC for acetylcholine (ACh), DOPAC and HVA levels. Simultaneously, recording of motor activity was performed. In the neurochemical postmortem tissue analysis we found no difference in any of the brain regions tested between isolated and group-reared animals. Amphetamine increased ACh levels in the mPFC, induced a decrease in DOPAC and HVA levels, and increased motor activity. A close to significant Drug x Housing interaction reflected the fact that the amphetamine-induced decrease of DOPAC was confined to the group-housed animals. In conclusion, social isolation leads only to moderate changes in the dopaminergic system in the mPFC, whereas the cholinergic system remains unaffected.
Leng
Andreas
A
Behavioral Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603, Schwerzenbach, Switzerland.
Feldon
Joram
J
Ferger
Boris
B
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002421:Caudate Nucleus / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D017551:Microdialysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009714:Nucleus Accumbens / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012934:Social Isolation; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D003913:Dextroamphetamine; D004298:Dopamine; D006719:Homovanillic Acid