TY - JOUR
T1 - Environmental enrichment enhances sensitization to GBR 12935-induced activity and decreases dopamine transporter function in the medial prefrontal cortex
AU - Zhu, Jun
AU - Green, Thomas
AU - Bardo, Michael T.
AU - Dwoskin, Linda P.
N1 - Funding Information:
This research was supported by NIH Grants DA12964, DA05312, DA06093 and DA00399.
PY - 2004/1/5
Y1 - 2004/1/5
N2 - Rats raised in an enriched condition (EC) during development display increased hyperactivity to the effect of acute amphetamine compared to rats raised in an impoverished condition (IC). The present study determined whether environmental enrichment differentially alters the effects of GBR 12935 administration, a selective dopamine transporter (DAT) inhibitor. Acutely, EC rats showed a greater, dose-dependent GBR 12935-induced increase in activity compared to IC rats; however, basal activity for EC rats was lower than for IC rats. After repeated GBR 12935, only EC rats exhibited behavioral sensitization. Kinetic analysis of DAT function in medial prefrontal cortex (mPFC) revealed that the maximal velocity of [3H]dopamine ([3H]DA) uptake in EC rats was less than in IC rats (4.9±0.6 and 7.7±0.6pmol/min/ mg, respectively), but not in striatum or nucleus accumbens. Furthermore, GBR 12935-induced inhibition of DAT function, [3H]GBR 12935 binding density and DA content in mPFC, striatum and nucleus accumbens were not different between EC and IC rats. However, dihydroxyphenylacetic acid content in mPFC was lower in EC than IC rats, whereas no differences were found in striatum and nucleus accumbens. These results suggest that EC-induced changes in activity may be due to decreased DAT function and decreased DA metabolism in the mPFC.
AB - Rats raised in an enriched condition (EC) during development display increased hyperactivity to the effect of acute amphetamine compared to rats raised in an impoverished condition (IC). The present study determined whether environmental enrichment differentially alters the effects of GBR 12935 administration, a selective dopamine transporter (DAT) inhibitor. Acutely, EC rats showed a greater, dose-dependent GBR 12935-induced increase in activity compared to IC rats; however, basal activity for EC rats was lower than for IC rats. After repeated GBR 12935, only EC rats exhibited behavioral sensitization. Kinetic analysis of DAT function in medial prefrontal cortex (mPFC) revealed that the maximal velocity of [3H]dopamine ([3H]DA) uptake in EC rats was less than in IC rats (4.9±0.6 and 7.7±0.6pmol/min/ mg, respectively), but not in striatum or nucleus accumbens. Furthermore, GBR 12935-induced inhibition of DAT function, [3H]GBR 12935 binding density and DA content in mPFC, striatum and nucleus accumbens were not different between EC and IC rats. However, dihydroxyphenylacetic acid content in mPFC was lower in EC than IC rats, whereas no differences were found in striatum and nucleus accumbens. These results suggest that EC-induced changes in activity may be due to decreased DAT function and decreased DA metabolism in the mPFC.
KW - Activity
KW - Dopamine transporter
KW - Dopamine uptake
KW - Environmental enrichment
KW - GBR 12935
KW - Medial prefrontal cortex
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U2 - 10.1016/S0166-4328(03)00190-6
DO - 10.1016/S0166-4328(03)00190-6
M3 - Article
C2 - 14684252
AN - SCOPUS:0346134979
SN - 0166-4328
VL - 148
SP - 107
EP - 117
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1-2
ER -