The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats
- First Online:
- 156 Downloads
We have previously reported that selective antagonism of brain D3 receptors by SB-277011A or NGB 2904 significantly attenuates cocaine- or nicotine-enhanced brain stimulation reward (BSR).
In the present study, we investigated whether the selective D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 agonist BP-897 similarly reduce methamphetamine (METH)-enhanced BSR.
Materials and methods
Rats were trained to respond for rewarding electrical self-stimulation of the medial forebrain bundle. To assess the degree of drug-induced changes in BSR, a rate–frequency curve shift paradigm was used to measure brain-reward threshold (θ0).
METH (0.1–0.65 mg/kg, i.p.) dose-dependently lowered (∼10–50%) BSR thresholds, producing an enhancement of BSR. Pretreatment with SB-277011A (12 mg/kg, but not 24 mg/kg, i.p.) significantly attenuated METH-enhanced BSR. NGB 2904 (0.1–1.0 mg/kg, but not 10 mg/kg) also attenuated METH-enhanced BSR. SB-277011A or NGB 2904 alone, at the doses tested, had no effect on BSR. Pretreatment with BP-897 (0.1–5 mg/kg) dose-dependently attenuated METH-enhanced BSR. However, when the dose was increased to 10 mg/kg, BP-897 shifted the stimulation–response curve to the right (inhibited BSR itself) in the presence or absence of METH.
Selective antagonism of D3 receptors by SB-277011A or NGB 2904 attenuates METH-enhanced BSR in rats, while the METH-enhanced BSR attenuation produced by BP-897 may involve both D3 and non-D3 receptors. These findings support a potential use of selective D3 receptor antagonists for the treatment of METH addiction.
KeywordsMethamphetamine Dopamine D3 receptor Brain reward SB-277011A NGB 2904 BP-897
- Campiani G, Butini S, Trotta F, Fattorusso C, Catalanotti B, Aiello F, Gemma S, Nacci V, Novellino E, Stark JA, Cagnotto A, Fumagalli E, Carnovali F, Cervo L, Mennini T (2003) Synthesis and pharmacological evaluation of potent and highly selective D3 receptor ligands: inhibition of cocaine-seeking behavior and the role of dopamine D3/D2 receptors. J Med Chem 46:3822–3839PubMedCrossRefGoogle Scholar
- Campos AC, Xi Z-X, Gilbert J, Ashby CR Jr, Heidbreder CA, Newman AH, Gardner EL (2004) Blockade of dopamine D3 receptors by SB-277011A, NGB 2904 or BP 897 attenuates nicotine-enhanced brain stimulation reward in rat. Abstracts of the 34th Annual Meeting of the Society for Neuroscience; 2004 November 23–27; San Diego, CA. 2004 Abstract Viewer/Itinerary Planner. Online. Society for Neuroscience, Washington, DC. Abstract 691.6Google Scholar
- Dillon C, Li X, Ashby CR Jr, Heidbreder CA, Gaál J, Xi ZX, Gardner EL (2007) The dopamine D3 receptor antagonist SB-277011A potentiates cocaine-induced increases in extracellular dopamine in the nucleus accumbens in rats. Abstracts of the 37th Annual Meeting for Society of Neuroscience; 2007 November 3–7 San Diego, CAGoogle Scholar
- Duarte C, Lefebvre C, Chaperon F, Hamon M, Thiébot M-H (2003) Effects of a dopamine D3 receptor ligand, BP 897, on acquisition and expression of food-, morphine-, and cocaine-induced conditioned place preference, and food-seeking behavior in rats. Neuropsychopharmacology 28:1903–1915PubMedGoogle Scholar
- Ikemoto S (2007) Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex. Brain Res Rev (in press)Google Scholar
- National Academy of Sciences (National Research Council, Commission on Life Sciences, Institute of Laboratory Animal Resources) (1996) Guide for the Care and Use of Laboratory Animals. National Academy Press: Washington DCGoogle Scholar
- Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic, San DiegoGoogle Scholar
- Stanwood GD, Artymyshyn RP, Kung M-P, Kung HF, Lucki I, McGonigle P (2000) Quantitative autoradiographic mapping of rat brain dopamine D3 binding with [125I]7-OH-PIPAT: evidence for the presence of D3 receptors on dopaminergic and nondopaminergic cell bodies and terminals. J Pharmacol Exp Ther 295:1223–1231PubMedGoogle Scholar
- Stemp G, Ashmeade T, Branch CL, Hadley MS, Hunter AJ, Johnson CN, Nash DJ, Thewlis KM, Vong AKK, Austin NE (2000) Design and synthesis of trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide (SB-277011): a potent and selective dopamine D3 receptor antagonist with high oral bioavailability and CNS penetration in the rat. J Med Chem 43:1878–1885PubMedCrossRefGoogle Scholar
- Xi Z-X, Gilbert JG, Pak AC, Ashby CR Jr, Heidbreder CA, Gardner EL (2005) Selective dopamine D3 receptor antagonism by SB-277011A attenuates cocaine reinforcement as assessed by progressive-ratio and variable-cost–variable-payoff fixed-ratio cocaine self-administration in rats. Eur J Neurosci 21:3427–3438PubMedCrossRefGoogle Scholar
- Xi Z-X, Newman AH, Gilbert JG, Pak AC, Peng X-Q, Ashby CR Jr, Gitajn L, Gardner EL (2006) The novel dopamine D3 receptor antagonist NGB 2904 inhibits cocaine’s rewarding effects and cocaine-induced reinstatement of drug-seeking behavior in rats. Neuropsychopharmacology 31:1393–1405PubMedCrossRefGoogle Scholar