Effect of environmental enrichment on methylphenidate-induced locomotion and dopamine transporter dynamics

Thomas E. Wooters; Michael T. Bardo; Linda P. Dwoskin; Narasimha M. Midde; Adrian M. Gomez; Charles F. Mactutus; Rosemarie M. Booze; Jun Zhu

doi:10.1016/j.bbr.2011.01.001

Effect of environmental enrichment on methylphenidate-induced locomotion and dopamine transporter dynamics

Thomas E. Wooters, Michael T. Bardo, Linda P. Dwoskin, Narasimha M. Midde, Adrian M. Gomez, Charles F. Mactutus, Rosemarie M. Booze, Jun Zhu

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Rats raised in an enriched condition (EC) are less sensitive to the locomotor effects of stimulant drugs than rats raised in an impoverished condition (IC). Methylphenidate (MPD), a primary pharmacotherapy for attention-deficit/hyperactivity disorder, has abuse potential. This study determined whether environmental enrichment differentially altered the effects of MPD on locomotor activity and dopamine (DA) transporter (DAT) function. Acute and repeated MPD (3 or 10mg/kg, s.c.) increased locomotion in EC, IC and social condition (SC) rats; however, EC rats showed a blunted response to repeated MPD (3mg/kg). The maximal velocity (V _max) of [ ³H]DA uptake in the presence of the combination of phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator and okadaic acid, a protein phosphatase inhibitor was decreased in EC and IC rats by 68% and 40%, respectively, indicating that DAT in prefrontal cortex (PFC) is more sensitive to PKC-mediated down-regulation in EC rats. Acute MPD (10mg/kg) administration decreased the V _max of [ ³H]DA uptake in PFC and striatum in EC rats, but not in IC rats. Furthermore, [ ³H]WIN 35,428 binding density was decreased in PFC of EC and IC rats, and in striatum of EC rats given repeated MPD (10mg/kg). These results demonstrate that environmental enrichment modulates DAT dynamics in PFC. However, since the change in DAT function was observed only following the high dose of MPH (10mg/kg), the attenuated locomotor response to repeated MPD (3mg/kg) in EC rats is not likely due to a specific DAT alteration in the brain regions examined.

Original language	English
Pages (from-to)	98-107
Number of pages	10
Journal	Behavioural Brain Research
Volume	219
Issue number	1
DOIs	https://doi.org/10.1016/j.bbr.2011.01.001
State	Published - May 16 2011

Bibliographical note

Funding Information:
This work was supported by grants from the National Institute on Drug Abuse : DA024275 (J.Z.), DA026721 (J.Z.), DA012964 (M.T.B.), DA013137 (R.M.B.) and DA023853 (T.E.W.) as well as a University of Kentucky Research Support grant (J.Z.). We acknowledge Dr. Maarten E.A. Reith (New York University, New York, NY) for commenting on the manuscript.

Keywords

Behavioral sensitization
Dopamine transporter
Environmental enrichment
Methylphenidate
Prefrontal cortex
Protein kinase C

ASJC Scopus subject areas

Behavioral Neuroscience

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10.1016/j.bbr.2011.01.001

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title = "Effect of environmental enrichment on methylphenidate-induced locomotion and dopamine transporter dynamics",

abstract = "Rats raised in an enriched condition (EC) are less sensitive to the locomotor effects of stimulant drugs than rats raised in an impoverished condition (IC). Methylphenidate (MPD), a primary pharmacotherapy for attention-deficit/hyperactivity disorder, has abuse potential. This study determined whether environmental enrichment differentially altered the effects of MPD on locomotor activity and dopamine (DA) transporter (DAT) function. Acute and repeated MPD (3 or 10mg/kg, s.c.) increased locomotion in EC, IC and social condition (SC) rats; however, EC rats showed a blunted response to repeated MPD (3mg/kg). The maximal velocity (V max) of [ 3H]DA uptake in the presence of the combination of phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator and okadaic acid, a protein phosphatase inhibitor was decreased in EC and IC rats by 68% and 40%, respectively, indicating that DAT in prefrontal cortex (PFC) is more sensitive to PKC-mediated down-regulation in EC rats. Acute MPD (10mg/kg) administration decreased the V max of [ 3H]DA uptake in PFC and striatum in EC rats, but not in IC rats. Furthermore, [ 3H]WIN 35,428 binding density was decreased in PFC of EC and IC rats, and in striatum of EC rats given repeated MPD (10mg/kg). These results demonstrate that environmental enrichment modulates DAT dynamics in PFC. However, since the change in DAT function was observed only following the high dose of MPH (10mg/kg), the attenuated locomotor response to repeated MPD (3mg/kg) in EC rats is not likely due to a specific DAT alteration in the brain regions examined.",

keywords = "Behavioral sensitization, Dopamine transporter, Environmental enrichment, Methylphenidate, Prefrontal cortex, Protein kinase C",

author = "Wooters, {Thomas E.} and Bardo, {Michael T.} and Dwoskin, {Linda P.} and Midde, {Narasimha M.} and Gomez, {Adrian M.} and Mactutus, {Charles F.} and Booze, {Rosemarie M.} and Jun Zhu",

note = "Funding Information: This work was supported by grants from the National Institute on Drug Abuse : DA024275 (J.Z.), DA026721 (J.Z.), DA012964 (M.T.B.), DA013137 (R.M.B.) and DA023853 (T.E.W.) as well as a University of Kentucky Research Support grant (J.Z.). We acknowledge Dr. Maarten E.A. Reith (New York University, New York, NY) for commenting on the manuscript.",

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AU - Bardo, Michael T.

AU - Dwoskin, Linda P.

AU - Midde, Narasimha M.

AU - Gomez, Adrian M.

AU - Mactutus, Charles F.

AU - Booze, Rosemarie M.

AU - Zhu, Jun

N1 - Funding Information: This work was supported by grants from the National Institute on Drug Abuse : DA024275 (J.Z.), DA026721 (J.Z.), DA012964 (M.T.B.), DA013137 (R.M.B.) and DA023853 (T.E.W.) as well as a University of Kentucky Research Support grant (J.Z.). We acknowledge Dr. Maarten E.A. Reith (New York University, New York, NY) for commenting on the manuscript.

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N2 - Rats raised in an enriched condition (EC) are less sensitive to the locomotor effects of stimulant drugs than rats raised in an impoverished condition (IC). Methylphenidate (MPD), a primary pharmacotherapy for attention-deficit/hyperactivity disorder, has abuse potential. This study determined whether environmental enrichment differentially altered the effects of MPD on locomotor activity and dopamine (DA) transporter (DAT) function. Acute and repeated MPD (3 or 10mg/kg, s.c.) increased locomotion in EC, IC and social condition (SC) rats; however, EC rats showed a blunted response to repeated MPD (3mg/kg). The maximal velocity (V max) of [ 3H]DA uptake in the presence of the combination of phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator and okadaic acid, a protein phosphatase inhibitor was decreased in EC and IC rats by 68% and 40%, respectively, indicating that DAT in prefrontal cortex (PFC) is more sensitive to PKC-mediated down-regulation in EC rats. Acute MPD (10mg/kg) administration decreased the V max of [ 3H]DA uptake in PFC and striatum in EC rats, but not in IC rats. Furthermore, [ 3H]WIN 35,428 binding density was decreased in PFC of EC and IC rats, and in striatum of EC rats given repeated MPD (10mg/kg). These results demonstrate that environmental enrichment modulates DAT dynamics in PFC. However, since the change in DAT function was observed only following the high dose of MPH (10mg/kg), the attenuated locomotor response to repeated MPD (3mg/kg) in EC rats is not likely due to a specific DAT alteration in the brain regions examined.

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Effect of environmental enrichment on methylphenidate-induced locomotion and dopamine transporter dynamics

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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