TY - JOUR
T1 - Isolation rearing as a preclinical model of attention/deficit-hyperactivity disorder
AU - Yates, Justin R.
AU - Darna, Mahesh
AU - Gipson, Cassandra D.
AU - Dwoskin, Linda P.
AU - Bardo, Michael T.
N1 - Funding Information:
This research was funded by NIH grants P50 DA05312 , R01 DA12964 and R01 DA11716 .
PY - 2012/10/1
Y1 - 2012/10/1
N2 - Rats raised in an isolated condition (IC) are impulsive and hyperactive compared to rats raised in an enriched condition (EC), suggesting that isolation rearing may be a preclinical model of attention-deficit/hyperactivity disorder (ADHD). The current study determined if administration of methylphenidate (MPH), a dopamine transporter (DAT) blocker used in the treatment of ADHD, reduces the hyperactivity observed in IC rats toward levels observed in EC rats. Another goal was to determine if chronic MPH treatment differentially alters DAT function in EC and IC rats in medial prefrontal cortex (mPFC) or orbitofrontal cortex (OFC). IC and EC rats were treated with either MPH (1.5mg/kg, p.o.) or vehicle from postnatal days (PND) 28-51. On PND 28 and 51, rats were evaluated for MPH-induced locomotor activity. On PND 55-63, in vitro [3H]DA uptake assays were performed in mPFC and OFC. At both PND 28 and 51, IC rats were hyperactive compared to EC rats. At PND 28, MPH increased activity in EC rats only. At PND 51, MPH did not alter locomotor activity in IC or EC rats. Beginning at PND 55, basal uptake of [3H]dopamine in IC rats was higher in mPFC and lower in OFC compared to EC rats. The basal differences in DAT function were normalized by MPH treatment in mPFC, but not in OFC. These findings suggest that isolation rearing may not represent a valid predictive model for screening effective medications in the treatment of hyperactivity associated with ADHD.
AB - Rats raised in an isolated condition (IC) are impulsive and hyperactive compared to rats raised in an enriched condition (EC), suggesting that isolation rearing may be a preclinical model of attention-deficit/hyperactivity disorder (ADHD). The current study determined if administration of methylphenidate (MPH), a dopamine transporter (DAT) blocker used in the treatment of ADHD, reduces the hyperactivity observed in IC rats toward levels observed in EC rats. Another goal was to determine if chronic MPH treatment differentially alters DAT function in EC and IC rats in medial prefrontal cortex (mPFC) or orbitofrontal cortex (OFC). IC and EC rats were treated with either MPH (1.5mg/kg, p.o.) or vehicle from postnatal days (PND) 28-51. On PND 28 and 51, rats were evaluated for MPH-induced locomotor activity. On PND 55-63, in vitro [3H]DA uptake assays were performed in mPFC and OFC. At both PND 28 and 51, IC rats were hyperactive compared to EC rats. At PND 28, MPH increased activity in EC rats only. At PND 51, MPH did not alter locomotor activity in IC or EC rats. Beginning at PND 55, basal uptake of [3H]dopamine in IC rats was higher in mPFC and lower in OFC compared to EC rats. The basal differences in DAT function were normalized by MPH treatment in mPFC, but not in OFC. These findings suggest that isolation rearing may not represent a valid predictive model for screening effective medications in the treatment of hyperactivity associated with ADHD.
KW - Attention-deficit/hyperactivity disorder
KW - Dopamine transporter
KW - Isolation rearing
KW - Locomotor activity
KW - Methylphenidate
KW - Rat
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UR - http://www.scopus.com/inward/citedby.url?scp=84864400999&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2012.04.043
DO - 10.1016/j.bbr.2012.04.043
M3 - Article
C2 - 22580232
AN - SCOPUS:84864400999
SN - 0166-4328
VL - 234
SP - 292
EP - 298
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -