pubmed.ncbi.nlm.nih.gov

Role of the dopamine D3 receptor in reactivity to cocaine-associated cues in mice - PubMed

Role of the dopamine D3 receptor in reactivity to cocaine-associated cues in mice

Bernard Le Foll et al. Eur J Neurosci. 2002 Jun.

Abstract

Environmental stimuli previously associated with drug effects can acquire secondary reinforcing properties, able to maintain drug-seeking behaviour or induce relapse. We have used a classical Pavlovian conditioning procedure to assess the role of the dopamine D3 receptor (D3R) in the expression of drug-conditioned responses. Mice repeatedly receiving cocaine in a particular environment distinct from home-cages displayed hyperlocomotion after subsequent exposure to the drug-paired environment. Cocaine-conditioned hyperactivity was inhibited by BP 897 or SB-277011-A, D3R-selective partial agonist and antagonist, respectively. D3R gene-targeted mice showed a trend towards an increase in cocaine cue-conditioned hyperactivity. BP 897 had no effect on reactivity to neutral or aversive cues. Cocaine-conditioned mice had increased levels of D3R mRNA and binding in the nucleus accumbens (NAc), and transcripts of brain-derived neurotrophic factor (BDNF), a factor controlling D3R expression, in the ventral tegmental area (VTA). Cocaine had no effects on D3R or BDNF genes when administered in home-cages. Cocaine cue-conditioned c-fos expression was found in cortical areas, notably in the somatosensory cortex, where it was inhibited by BP 897, and in several regions belonging or linked to the limbic system. In conditioned mice, BP 897 inhibited c-fos expression in VTA and activated it in amygdala. These results demonstrate a modulation of reactivity to cocaine cues by the D3R, the expression of which is elevated in the NAc by the repeated association of drug effects with a particular context, through a BDNF-dependent mechanism. D3R-selective partial agonist or antagonist inhibit cocaine cue-conditioned activity possibly by normalizing exacerbated D3R function in the NAc, but our results also point to a possible participation of a pathway involving the VTA, amygdala and somatosensory cortex.

PubMed Disclaimer

Cited by

Rationale in support of the use of selective dopamine D₃ receptor antagonists for the pharmacotherapeutic management of substance use disorders.
Heidbreder C. Heidbreder C. Naunyn Schmiedebergs Arch Pharmacol. 2013 Feb;386(2):167-76. doi: 10.1007/s00210-012-0803-6. Epub 2012 Oct 28. Naunyn Schmiedebergs Arch Pharmacol. 2013. PMID: 23104235 Review.
The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice.
Chang WL, Geyer MA, Buell MR, Weber M, Swerdlow NR. Chang WL, et al. Behav Pharmacol. 2010 Mar;21(2):135-43. doi: 10.1097/FBP.0b013e328337be7e. Behav Pharmacol. 2010. PMID: 20215963 Free PMC article.
Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress.
Guerrero-Bautista R, Franco-García A, Hidalgo JM, Fernández-Gómez FJ, Ribeiro Do Couto B, Milanés MV, Núñez C. Guerrero-Bautista R, et al. Int J Mol Sci. 2021 Mar 18;22(6):3100. doi: 10.3390/ijms22063100. Int J Mol Sci. 2021. PMID: 33803578 Free PMC article.
Nicotine induces conditioned place preferences over a large range of doses in rats.
Le Foll B, Goldberg SR. Le Foll B, et al. Psychopharmacology (Berl). 2005 Apr;178(4):481-92. doi: 10.1007/s00213-004-2021-5. Epub 2004 Nov 18. Psychopharmacology (Berl). 2005. PMID: 15765262
Gestational exposure to nicotine and monoamine oxidase inhibitors influences cocaine-induced locomotion in adolescent rats.
Franke RM, Belluzzi JD, Leslie FM. Franke RM, et al. Psychopharmacology (Berl). 2007 Nov;195(1):117-24. doi: 10.1007/s00213-007-0876-y. Epub 2007 Jul 26. Psychopharmacology (Berl). 2007. PMID: 17653695

Role of the dopamine D3 receptor in reactivity to cocaine-associated cues in mice - PubMed