Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic systems.
Isolation rearing of rats produces a behavioral syndrome indicative of altered dopamine (DA) function in the nucleus accumbens (NAC). The present experiments extend these findings by investigating: (a) interactions between isolation rearing and repeated handling/testing on presynaptic DA function in the NAC using in vivo microdialysis: (b) the dose-response curve for the effects of d-amphetamine, and the responses elicited by high potassium, using in vivo microdialysis, and (c) postsynaptic function in isolates as indexed by DA receptor-linked cAMP production. Experiment 1 showed that both isolation rearing and repeated handling/testing had effects on monoamine function in the NAC. However, while both manipulations enhanced DA release evoked by d-amphetamine, only isolated rats had elevated basal DA levels. Opposite neurochemical changes were observed with respect to the serotonin metabolite 5-HIAA, isolates having lower, and repeatedly handled/tested animals having higher, extracellular levels. Experiment 2 provided evidence for enhanced d-amphetamine-evoked DA release in isolated animals, while potassium-evoked DA release was reduced. Experiment 3 provided evidence that the isolation rearing induced changes in presynaptic DA function were accompanied by postsynaptic changes. Specifically, the inhibitory influence of the D2 receptor on D1 receptor-stimulated cAMP production was attenuated in ventral striatal slices taken from isolates, suggesting a functional downregulation of D2 receptors.
Hall
F S
FS
Department of Experimental Psychology, University of Cambridge, UK.
Wilkinson
L S
LS
Humby
T
T
Inglis
W
W
Kendall
D A
DA
Marsden
C A
CA
Robbins
T W
TW
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006234:Handling, Psychological; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D012934:Social Isolation; D013469:Sulpiride / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D013469:Sulpiride; D003913:Dextroamphetamine; D004298:Dopamine