Fos expression in response to dopamine D3-preferring phenylpiperazine drugs given with and without cocaine
Article first published online: 17 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 67, Issue 12, pages 847–855, December 2013
How to Cite
Nolan, B. C., Liu, S., Hammerslag, L. R., Cheung, T. H.C., Lenz, J., Mach, R. H., Luedtke, R. R. and Neisewander, J. L. (2013), Fos expression in response to dopamine D3-preferring phenylpiperazine drugs given with and without cocaine. Synapse, 67: 847–855. doi: 10.1002/syn.21691
- Issue published online: 15 OCT 2013
- Article first published online: 17 JUL 2013
- Accepted manuscript online: 13 JUN 2013 11:52PM EST
- Manuscript Accepted: 6 JUN 2013
- Manuscript Received: 7 FEB 2013
- NIDA. Grant Number: DA023957
- immediate early gene;
- nucleus accumbens
WC 44 and WC 10 are phenylpiperazines with low (23 fold) to moderate (42 fold) selectivity for dopamine D3 receptors (D3Rs) over D2Rs, respectively. WC 44 is a full D3R agonist in the forskolin-stimulated adenylyl cyclase (AC) assay, whereas WC 10 has little efficacy. In contrast to their opposite effects in the AC assay, these drugs often produce similar behavioral effects, suggesting that the AC assay does not predict the efficacy of these drugs in vivo. Here, we examined whether Fos protein expression induced by these drugs would be more consistent with their behavioral effects in vivo. Rats received either vehicle, WC 10 (5.6 mg/kg, i.p.), WC 44 (10.0 mg/kg, i.p), cocaine (10.0 mg/kg, i.p.), or cocaine with WC 10 (5.6 mg/kg, i.p.) or with WC 44 (10.0 mg/kg, i.p). Locomotion was monitored for 90 min and the brains were harvested for immunohistochemistry. Both WC 10 and WC 44 decreased spontaneous and cocaine-induced locomotion. Both compounds also increased Fos expression relative to saline in the dorsal striatum and nucleus accumbens core and shell, and relative to cocaine alone in the nucleus accumbens shell. The findings suggest that even though these compounds have different efficacy in the AC bioassy, they produce similar brain activation and attenuation of cocaine hyperlocomotion. Together with our previous research demonstrating that these compounds down-shift the cocaine self-administration dose-effect function, the findings support the idea that D3R-selective compounds may be useful for cocaine dependence medications development. Synapse 67:847–855, 2013. © 2013 Wiley Periodicals, Inc.