Tags

Type your tag names separated by a space and hit enter

Acute cocaine differentially alters accumbens and striatal dopamine clearance in low and high cocaine locomotor responders: behavioral and electrochemical recordings in freely moving rats.
J Pharmacol Exp Ther. 2002 Sep; 302(3):1201-11.JP

Abstract

Behavioral responses of rodents to cocaine are characterized by marked individual variability. Here, outbred male Sprague-Dawley rats were profiled based on concomitant recording of behavioral and electrochemical responses. Rats were categorized as either low or high cocaine responders (LCRs or HCRs, respectively) based on their differential locomotor responsiveness to an acute, low-dose injection of cocaine (10 mg/kg i.p.). LCRs and HCRs also differed in other cocaine-induced behaviors. The role of the dopamine transporter (DAT) in mediating the behavioral differences in cocaine responsiveness in LCRs and HCRs was investigated by high-speed chronoamperometric recording of exogenous dopamine (DA) clearance signals in nucleus accumbens (NAc) and dorsal striatum (dSTR). Higher volumes of DA were required in NAc of HCRs, than of LCRs, to produce equivalent peak DA signal amplitude (A(max)) responses. In HCRs, systemic cocaine administration evoked an immediate and prolonged 2-fold augmentation in A(max) in both brain regions, coincident with locomotor activation. The cocaine-induced decrease in the efficiency of DA clearance (k) in NAc of HCRs was more immediate and prolonged than in dSTR, where the transient decrease coincided with maximal stereotypic behavior. In contrast, in LCRs, A(max) was not altered by cocaine, and decay rate constant (k) was transiently attenuated only in dSTR. Correlation analyses of individual responses revealed that cocaine-induced changes in DA clearance signal parameters accounted for 20 to 40% of the variation in behavioral responsiveness to cocaine. Overall, our findings emphasize the importance of characterizing individual responses to understand more fully the range of functional consequences resulting from DAT inhibition.

Authors+Show Affiliations

Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA. jilla.sabeti@uchsc.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12183681

Citation

Sabeti, Jilla, et al. "Acute Cocaine Differentially Alters Accumbens and Striatal Dopamine Clearance in Low and High Cocaine Locomotor Responders: Behavioral and Electrochemical Recordings in Freely Moving Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 302, no. 3, 2002, pp. 1201-11.
Sabeti J, Gerhardt GA, Zahniser NR. Acute cocaine differentially alters accumbens and striatal dopamine clearance in low and high cocaine locomotor responders: behavioral and electrochemical recordings in freely moving rats. J Pharmacol Exp Ther. 2002;302(3):1201-11.
Sabeti, J., Gerhardt, G. A., & Zahniser, N. R. (2002). Acute cocaine differentially alters accumbens and striatal dopamine clearance in low and high cocaine locomotor responders: behavioral and electrochemical recordings in freely moving rats. The Journal of Pharmacology and Experimental Therapeutics, 302(3), 1201-11.
Sabeti J, Gerhardt GA, Zahniser NR. Acute Cocaine Differentially Alters Accumbens and Striatal Dopamine Clearance in Low and High Cocaine Locomotor Responders: Behavioral and Electrochemical Recordings in Freely Moving Rats. J Pharmacol Exp Ther. 2002;302(3):1201-11. PubMed PMID: 12183681.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acute cocaine differentially alters accumbens and striatal dopamine clearance in low and high cocaine locomotor responders: behavioral and electrochemical recordings in freely moving rats. AU - Sabeti,Jilla, AU - Gerhardt,Greg A, AU - Zahniser,Nancy R, PY - 2002/8/17/pubmed PY - 2002/9/19/medline PY - 2002/8/17/entrez SP - 1201 EP - 11 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 302 IS - 3 N2 - Behavioral responses of rodents to cocaine are characterized by marked individual variability. Here, outbred male Sprague-Dawley rats were profiled based on concomitant recording of behavioral and electrochemical responses. Rats were categorized as either low or high cocaine responders (LCRs or HCRs, respectively) based on their differential locomotor responsiveness to an acute, low-dose injection of cocaine (10 mg/kg i.p.). LCRs and HCRs also differed in other cocaine-induced behaviors. The role of the dopamine transporter (DAT) in mediating the behavioral differences in cocaine responsiveness in LCRs and HCRs was investigated by high-speed chronoamperometric recording of exogenous dopamine (DA) clearance signals in nucleus accumbens (NAc) and dorsal striatum (dSTR). Higher volumes of DA were required in NAc of HCRs, than of LCRs, to produce equivalent peak DA signal amplitude (A(max)) responses. In HCRs, systemic cocaine administration evoked an immediate and prolonged 2-fold augmentation in A(max) in both brain regions, coincident with locomotor activation. The cocaine-induced decrease in the efficiency of DA clearance (k) in NAc of HCRs was more immediate and prolonged than in dSTR, where the transient decrease coincided with maximal stereotypic behavior. In contrast, in LCRs, A(max) was not altered by cocaine, and decay rate constant (k) was transiently attenuated only in dSTR. Correlation analyses of individual responses revealed that cocaine-induced changes in DA clearance signal parameters accounted for 20 to 40% of the variation in behavioral responsiveness to cocaine. Overall, our findings emphasize the importance of characterizing individual responses to understand more fully the range of functional consequences resulting from DAT inhibition. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12183681/Acute_cocaine_differentially_alters_accumbens_and_striatal_dopamine_clearance_in_low_and_high_cocaine_locomotor_responders:_behavioral_and_electrochemical_recordings_in_freely_moving_rats_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12183681 DB - PRIME DP - Unbound Medicine ER -