TY - JOUR
T1 - Behavioral sensitization to cocaine in rats
T2 - Evidence for temporal differences in dopamine D 3 and D 2 receptor sensitivity
AU - Collins, Gregory T.
AU - Truong, Yen Nhu Thi
AU - Levant, Beth
AU - Chen, Jianyong
AU - Wang, Shaomeng
AU - Woods, James H.
N1 - Funding Information:
This research was supported by USPHS NIDA grants DA 020669 and F013771, as well as HD02528. We acknowledge with appreciation the technical assistance of Davina Barron. G.T.Collins(*).Y.N.-T.Truong.S.Wang.J.H.Woods Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, 1150W. Medical Center Drive, Ann Arbor, MI 48109-0632, USA e-mail: [email protected]
PY - 2011/6
Y1 - 2011/6
N2 - Rationale Cocaine-induced changes in D 2 receptors have been implicated in the expression of sensitized behavioral responses and addiction-like behaviors; however, the influence of D 3 receptors is less clear. Objectives To characterize the effects of repeated cocaine administration on the sensitivity of rats to D 2- and D 3-mediated behaviors, as well as the binding properties of ventral striatal D 2-like and D 3 receptors. Methods Pramipexole was used to assess the sensitivity of rats to D 3/D 2 agonist-induced yawning, hypothermia, and locomotor activity, 24 h, 72 h, 10, 21, and 42 days after repeated cocaine or saline administration. The locomotor effects of cocaine (42 day) and the binding properties of ventral striatal D 2-like and D 3 receptors (24 h and 42 days) were also evaluated. Results Cocaine-treated rats displayed an enhanced locomotor response to cocaine, as well as a progressive and persistent leftward/upward shift of the ascending limb (72 h-42 day) and leftward shift of the descending limb (42 days) of the pramipexole-induced yawning dose-response curve. Cocaine treatment also decreased Bmax and K d for D 2-like receptors and increased D 3 receptor binding at 42 days. Cocaine treatment did not change pramipexole-induced hypothermia or locomotor activity or yawning induced by cholinergic or serotonergic agonists. Conclusions These studies suggest that temporal differences exist in the development of cocaine-induced sensitization of D 3 and D 2 receptors, with enhancements of D 3-mediated behavioral effects observed within 72 h and enhancements of D 2-mediated behavioral effects apparent 42 days after cocaine. These findings highlight the need to consider changes in D 3 receptor function when thinking about the behavioral plasticity that occurs during abstinence from cocaine use.
AB - Rationale Cocaine-induced changes in D 2 receptors have been implicated in the expression of sensitized behavioral responses and addiction-like behaviors; however, the influence of D 3 receptors is less clear. Objectives To characterize the effects of repeated cocaine administration on the sensitivity of rats to D 2- and D 3-mediated behaviors, as well as the binding properties of ventral striatal D 2-like and D 3 receptors. Methods Pramipexole was used to assess the sensitivity of rats to D 3/D 2 agonist-induced yawning, hypothermia, and locomotor activity, 24 h, 72 h, 10, 21, and 42 days after repeated cocaine or saline administration. The locomotor effects of cocaine (42 day) and the binding properties of ventral striatal D 2-like and D 3 receptors (24 h and 42 days) were also evaluated. Results Cocaine-treated rats displayed an enhanced locomotor response to cocaine, as well as a progressive and persistent leftward/upward shift of the ascending limb (72 h-42 day) and leftward shift of the descending limb (42 days) of the pramipexole-induced yawning dose-response curve. Cocaine treatment also decreased Bmax and K d for D 2-like receptors and increased D 3 receptor binding at 42 days. Cocaine treatment did not change pramipexole-induced hypothermia or locomotor activity or yawning induced by cholinergic or serotonergic agonists. Conclusions These studies suggest that temporal differences exist in the development of cocaine-induced sensitization of D 3 and D 2 receptors, with enhancements of D 3-mediated behavioral effects observed within 72 h and enhancements of D 2-mediated behavioral effects apparent 42 days after cocaine. These findings highlight the need to consider changes in D 3 receptor function when thinking about the behavioral plasticity that occurs during abstinence from cocaine use.
KW - Cocaine
KW - Dopamine D receptor
KW - Dopamine D2 receptor
KW - Pramipexole
KW - Sensitization
KW - Yawning
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U2 - 10.1007/s00213-010-2154-7
DO - 10.1007/s00213-010-2154-7
M3 - Article
C2 - 21207013
AN - SCOPUS:80052883235
SN - 0033-3158
VL - 215
SP - 609
EP - 620
JO - Psychopharmacology
JF - Psychopharmacology
IS - 4
ER -