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. 2007 Jan;86(1):37-44.
doi: 10.1016/j.pbb.2006.12.005. Epub 2006 Dec 20.

Low and high locomotor responsiveness to cocaine predicts intravenous cocaine conditioned place preference in male Sprague-Dawley rats

Affiliations

Low and high locomotor responsiveness to cocaine predicts intravenous cocaine conditioned place preference in male Sprague-Dawley rats

Richard M Allen et al. Pharmacol Biochem Behav. 2007 Jan.

Abstract

Outbred, male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on cocaine-induced locomotor activity in an open-field arena. This difference reflects cocaine's ability to inhibit the striatal dopamine transporter and predicts development of sensitization. To investigate the relationship between initial cocaine locomotor responsiveness and cocaine reward, here we first classified rats as either LCRs or HCRs in a conditioned place preference (CPP) apparatus. Subsequently, we conducted cocaine conditioning trials, twice-daily over 4 days with vehicle and cocaine (10 mg/kg, i.p. or 1 mg/kg, i.v.). When cocaine was administered by the i.p. route, similar to previous findings in the open-field, LCRs and HCRs were readily classified and locomotor sensitization developed in LCRs, but not HCRs. However, cocaine CPP was not observed. In contrast, when cocaine was administered by the i.v. route, the LCR/HCR classification not only predicted sensitization, but also CPP, with only LCR rats exhibiting sensitization and cocaine conditioning. Our findings show that the initial locomotor response to cocaine can predict CPP in male Sprague-Dawley rats under conditions when place conditioning develops, and that LCRs may be more prone to develop conditioning in the context of cocaine reward.

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Figures

Figure 1
Figure 1
Repeated i.p. cocaine injections induce locomotor sensitization in LCRs, but not in HCRs, when locomotor activity is measured in a CPP apparatus. Vehicle or cocaine (10 mg/kg, i.p.) was administered once daily for seven days to the control and experimental groups, respectively. Ordinate: Locomotor Activity Score, representing consecutive beam breaks in the CPP apparatus during the 30-min post-injection interval. Abscissa: Session. On day 8 for a reversal test (R), rats in the control group (n=4) were given cocaine whereas LCRs (n=6) and HCRs (n=6) were given vehicle. Mean values ± SEM. +++, p < 0.001, control vs. LCR; #, p < 0.05, control vs. HCR; ##, p < 0.01, control vs. HCR; ** p<0.01, LCR vs. HCR. Although significant between group differences were revealed by ANOVA at sessions one, four, five, six and seven, only post-hoc comparisons at sessions one and seven are presented on the figure.
Figure 2
Figure 2
Time course of locomotor activity in the CPP apparatus during sessions one and six of an experiment in which locomotor activity was measured in a place conditioning apparatus before and after place conditioning trials with i.p. vehicle or cocaine (10 mg/kg; panels A and C) or i.v. vehicle or cocaine (1 mg/kg; panels B and D). A separate group of rats was either injected i.p. or infused i.v. with vehicle in both compartments of the conditioning apparatus as an additional experimental control (“control”). Ordinates: Locomotor Activity Score, representing consecutive beam breaks in the CPP apparatus during 10 min bins. Abscissa: Time, in minutes. Arrows at 60 min indicate the time at which cocaine or vehicle was administered to rats. Mean values ± SEM. +, p < 0.05, control vs. LCR; ++, p < 0.01, control vs. LCR; #, p < 0.05, control vs. HCR; ##, p < 0.01, control vs. HCR; ### p < 0.001, control vs. HCR; *, p < 0.05 LCR vs. HCR; ***, p < 0.001 LCR vs. HCR.
Figure 3
Figure 3
Time course of locomotor activity in the CPP apparatus during the three min prior to and 10 min after i.p. injection (left panel) or i.v. infusion (right panel) of cocaine or vehicle (“control”) during session one. Ordinates: Locomotor Activity Score, representing consecutive beam breaks in the CPP apparatus during one-min bins. Abscissa: Time, in minutes. Arrows at 60 min indicate the time at which cocaine or vehicle was administered to rats. Mean values ± SEM. Results of select post-hoc comparisons are presented in the text.
Figure 4
Figure 4
LCRs, but not HCRs, show CPP after i.v. cocaine conditioning. Pre- and post-conditioning preference ratios [time in drug paired compartment / (time in drug and vehicle paired compartments)] calculated after four twice-daily conditioning trials with once-daily i.v. infusions of cocaine (1 mg/kg) and vehicle (or vehicle and vehicle for control rats). For between-group post-hoc comparisons of post-conditioning preference ratios, +, p < 0.01, control vs. LCR; *, p < 0.05, LCR vs. HCR. For within-group comparisons of pre- versus post-conditioning preference ratios, @, p < 0.05; @@@, p < 0.001.

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