PMID- 22394078 OWN - NLM STAT- MEDLINE DCOM- 20120827 LR - 20150708 IS - 1460-9568 (Electronic) IS - 0953-816X (Linking) VI - 35 IP - 8 DP - 2012 Apr TI - Lentiviral-mediated gene delivery reveals distinct roles of nucleus accumbens dopamine D2 and D3 receptors in novelty- and light-induced locomotor activity. PG - 1344-53 LID - 10.1111/j.1460-9568.2012.08028.x [doi] AB - The importance of the dopaminergic system for proper brain activity is demonstrated by findings that alterations in this system lead to severe disabilities, including motor impairment observed in various neurological and psychiatric disorders. Although the roles of specific dopamine receptors in behaviour have been extensively investigated using pharmacological agents and knockout mice, non-specificity of ligands and compensatory molecular adaptations in mutated animals restrict the interpretation of the results. To overcome these limitations and further explore the role of the dopamine D2 and D3 receptors (D2R and D3R) in rats, we used lentivirus-mediated gene knockdown and overexpression to specifically manipulate expression levels of these genes in the rat nucleus accumbens (NAcc), a brain area important for spontaneous and induced locomotor responses. Lentiviruses, inducing expression of rat D2R or D3R, or efficient knockdown of either receptor by small hairpin (sh)RNAs, were stereotaxically injected into the NAcc. While knockdown of either receptor significantly reduced spontaneous locomotor activity in a novel but not in a habituated environment, D2R and D3R appeared to contribute in opposite ways to light-induced locomotor activity. D2R knockdown increased while D3R knockdown decreased locomotor activity in this test. Altogether, our findings suggest that D2R and D3R, expressed in the NAcc, have both shared and non-overlapping roles in transduction of alerting signals elicited by potentially important sensory and environmental cues. CI - (c) 2012 The Authors. European Journal of Neuroscience (c) 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. FAU - Fernandes, Alinda R AU - Fernandes AR AD - MRC-SGDP-Centre, Institute of Psychiatry, King's College London, De Crespigny Park, PO80, London SE5 8AF, UK. FAU - Easton, Alanna C AU - Easton AC FAU - De Souza Silva, Maria A AU - De Souza Silva MA FAU - Schumann, Gunter AU - Schumann G FAU - Muller, Christian P AU - Muller CP FAU - Desrivieres, Sylvane AU - Desrivieres S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120307 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Receptors, Dopamine D2) RN - 0 (Receptors, Dopamine D3) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Cell Line, Transformed MH - Exploratory Behavior/*physiology MH - Gene Expression Regulation/genetics MH - Gene Transfer Techniques MH - Genetic Vectors/physiology MH - Green Fluorescent Proteins/genetics MH - Humans MH - Lentivirus/genetics MH - Light MH - Male MH - Maze Learning/physiology MH - Motor Activity/*physiology MH - Nucleus Accumbens/*metabolism MH - Rats MH - Receptors, Dopamine D2/genetics/*metabolism MH - Receptors, Dopamine D3/genetics/*metabolism MH - Transfection EDAT- 2012/03/08 06:00 MHDA- 2012/08/28 06:00 CRDT- 2012/03/08 06:00 PHST- 2012/03/08 06:00 [entrez] PHST- 2012/03/08 06:00 [pubmed] PHST- 2012/08/28 06:00 [medline] AID - 10.1111/j.1460-9568.2012.08028.x [doi] PST - ppublish SO - Eur J Neurosci. 2012 Apr;35(8):1344-53. doi: 10.1111/j.1460-9568.2012.08028.x. Epub 2012 Mar 7.