Differences in dopamine D1 and D2 binding between CD1 mice that respond and those that do not respond to cocaine-induced conditioned place preference

Ream Al-Hasani, Athanasios Metaxas, Alexis Bailey, Susanna Hourani, Ian Kitchen. University Of Surrey, Surrey, United Kingdom.

Within our laboratory we have found that cocaine-induced conditioned place preference (CPP) was not reliably observed in the CD1 strain of mouse. The response to cocaine-induced CPP was highly variable and we were able to divide the mice into responders and non-responders. We hypothesised that differences between components of the dopaminergic system of responders compared to non-responders may explain the cocaine-induced CPP difference in CD1 mice.

The mice were subcutaneously injected with 20 mg/kg cocaine and placed in the conditioning chamber every afternoon for 4 days. The pre-conditioning value (time spent in the drug paired chamber in seconds) was subtracted from the post-conditioning value to calculate a conditioning score (Soria et al. 2006). All mice with a score above 120 were assigned as responders. Those with a score between 10 and -50 were considered non-responders (n = 6). Following the CPP experiment quantitative autoradiography was carried out on the brains of these mice to study dopamine D1, D2 and DAT binding (Kitchen et al. 1997; Bailey et al. 2007) as well as dopamine D2 receptor-stimulated [35S] GTPγS binding (Bailey et al. 2008).

There was no difference in DAT binding or dopamine D2 activity between responders and non-responders in any brain region (P>0.05, two-way ANOVA). Significantly lower levels of dopamine D1 receptor binding was observed in the rostral caudate-putamen of responders (469.16±27 fmol/mg) compared to non-responders (552.49±22 fmol/mg) (P<0.001, Duncan’s post-hoc test). Moreover, significantly lower levels of dopamine D2 receptor binding were found in the caudal parts of the caudate-putamen in responders (38.38±4.91 fmol/mg) compared to non-responders (53.05±4.06 fmol/mg) (P<0.05 Duncan’s post-hoc analysis) and rostral parts of the caudate-putamen in responders (33.71±3.38 fmol/mg) compared to non-responders (47.07±1.86 fmol/mg) (P<0.001, Duncan’s post-hoc analysis).

The differences in DA D1 and DA D2 receptor binding between mice responding and not responding to cocaine-induced CPP suggest that the ability of cocaine to induce a rewarding effect may depend on dopamine D1 and D2 receptor density and/or D1 and D2 receptor regulation by cocaine. This might provide an important insight into the role of the dopaminergic system in the development of cocaine addiction.

Soria, G. et al (2006) Neuropsychopharmacology.31, 978-987.
Bailey A. et al (2007) Synapse. 61, 820-826.
Bailey A. et al (2008) Eur J Neurosci. 28, 759-770.
Kitchen I. et al (1997) Brain Res. 778, 73-88.