Advertisement

Brain Structure and Function

, Volume 223, Issue 3, pp 1313–1328 | Cite as

CART neurons in the lateral hypothalamus communicate with the nucleus accumbens shell via glutamatergic neurons in paraventricular thalamic nucleus to modulate reward behavior

  • Amit G. Choudhary
  • Amita R. Somalwar
  • Sneha Sagarkar
  • Abhishek Rale
  • Amul Sakharkar
  • Nishikant K. Subhedar
  • Dadasaheb M. Kokare
Original Article

Abstract

Paraventricular thalamic nucleus (PVT) serves as a transit node processing food and drug-associated reward information, but its afferents and efferents have not been fully defined. We test the hypothesis that the CART neurons in the lateral hypothalamus (LH) project to the PVT neurons, which in turn communicate via the glutamatergic fibers with the nucleus accumbens shell (AcbSh), the canonical site for reward. Rats conditioned to self-stimulate via an electrode in the right LH–medial forebrain bundle were used. Intra-PVT administration of CART (55–102) dose-dependently (10–50 ng/rat) lowered intracranial self-stimulation (ICSS) threshold and increased lever press activity, suggesting reward-promoting action of the peptide. However, treatment with CART antibody (intra-PVT) or MK-801 (NMDA antagonist, intra-AcbSh) produced opposite effects. A combination of sub-effective dose of MK-801 (0.01 µg/rat, intra-AcbSh) and effective dose of CART (25 ng/rat, intra-PVT) attenuated CART’s rewarding action. Further, we screened the LH–PVT–AcbSh circuit for neuroadaptive changes induced by conditioning experience. A more than twofold increase was noticed in the CART mRNA expression in the LH on the side ipsilateral to the implanted electrode for ICSS. In addition, the PVT of conditioned rats showed a distinct increase in the (a) c-Fos expressing cells and CART fiber terminals, and (b) CART and vesicular glutamate transporter 2 immunostained elements. Concomitantly, the AcbSh showed a striking increase in expression of NMDA receptor subunit NR1. We suggest that CART in LH–PVT and glutamate in PVT–AcbSh circuit might support food-seeking behavior under natural conditions and also store reward memory.

Keywords

CART Reward Intracranial self-stimulation Nucleus accumbens shell Paraventricular nucleus of thalamus Glutamate 

Notes

Acknowledgements

This work was supported by grants from the Science and Engineering Research Board (SERB) (SB/SO/AS-12/2014), Govt. of India, New Delhi, India to DMK. AJS acknowledges the grants from the UGC, Govt. of India, New Delhi, India [F.4-5/151-FRP/2014 (BSR)] and the BCUD, Savitribai Phule Pune University, Pune. AJS and SS also acknowledge the funds received from the DRDP of the Department of Biotechnology, Savitribai Phule Pune University, Pune, India. Confocal imaging was undertaken at IISER Pune Microscopy Facility, Pune, India.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

429_2017_1544_MOESM1_ESM.jpg (320 kb)
Supplementary Fig. 1. Schematic illustrations and representative photomicrographs of the brain sections of rat subjected to intracranial self-stimulation (ICSS) and pharmacological intervention in the paraventricular nucleus of thalamus (PVT). The position of the electrodes in lateral hypothalamus (LH)-medial forebrain bundle (MFB) region and the position of the cannulae in the PVT at various levels of brain sections are depicted with colored dots. These groups of rats with electrodes in the LH–MFB were used for administration of CART (at different doses) or CART antibody, in the PVT. Matching colored dots in ‘a’ and ‘b’ indicate the position of the two invasions (cannula and the electrode) in the same animal respectively (n = 5–6/group). Squares indicate the position of the electrode and cannulae that were not on the target, and the data from such animals were ignored. Coordinates along with the schematic sections indicate antero-posterior distance from bregma in millimeters (Paxinos and Watson 1998). 3 V, third ventricle; D3 V, dorsal third ventricle and f, fornix. (JPEG 319 kb)
429_2017_1544_MOESM2_ESM.jpg (273 kb)
Supplementary Fig. 2. Schematic illustrations and representative photomicrographs of the brain sections of rat subjected to intracranial self-stimulation (ICSS). The position of the electrodes in lateral hypothalamus (LH)-medial forebrain bundle (MFB) region ‘a’ and the position of the cannulae in the nucleus accumbens shell (AcbSh) ‘b’ is depicted with colored dots. These groups of rats with electrodes in the LH–MFB were used for administration of the vehicle and MK-801 in the AcbSh (a and b). Matching colored dots in ‘a’ and ‘b’ indicate the position of the two invasions (electrode and cannula) in the same animal, respectively (n = 5/group). Squares indicate the position of the electrode and cannulae that were not on the target, and the data from such animals were ignored. Coordinates along with the schematic sections indicate antero-posterior distance from bregma in millimeters (Paxinos and Watson 1998). aca, anterior commissure (anterior part); 3 V, third ventricle and f, fornix (JPEG 273 kb)
429_2017_1544_MOESM3_ESM.jpg (325 kb)
Supplementary Fig. 3. Schematic illustrations of the brain sections of rat subjected to intracranial self-stimulation (ICSS). Schematics in ‘a’, ‘b’ and ‘c’ represent the sections through the brains of rats showing the position of the electrodes in the LH–MFB (a) which were co-implanted with cannula in the AcbSh (b) and in the PVT (c) for MK-801 and CART administration, respectively (n = 5). This group was pre-treated with sub-effective dose of MK-801 (0.01 µg/rat, intra-AcbSh) prior to the effective dose of CART (25 ng/rat, intra-PVT). Squares indicate the position of the electrode and cannulae that were not on the target, and the data from such animals were ignored. Coordinates along with the schematic sections indicate antero-posterior distance from bregma in millimeters (Paxinos and Watson 1998). 3 V, third ventricle; aca, anterior commissure (anterior part); D3 V, dorsal third ventricle and f, fornix (JPEG 324 kb)
429_2017_1544_MOESM4_ESM.jpg (1.4 mb)
Supplementary Fig. 4. Neuronal projections from the paraventricular nucleus of thalamus (PVT) to the nucleus accumbens shell (AcbSh) as revealed by DiI. Schematic of rat brain showing the position of cannula, asterisk indicates the passage of the cannula used for DiI administration in AcbSh (a and a’). Low (b-e) magnification images of PVT [coordinates (AP: −1.8 mm to bregma);Paxinos and Watson (1998)] showing DiI-labeled fibers (b), CART fibers (c), DAPI (d) and overlay (e). Rectangles in b-e indicate the areas shown at higher magnification in b’-e’ respectively. Small arrows, Dil labeled fibers; arrowheads, CART fibers and large arrows, CART fibers in close vicinity of the DiI fibers. D3 V, dorsal third ventricle. Scale bar = 100 µm (b-e) and 50 µm (b’-e’) (JPEG 1406 kb)

References

  1. Bespalov AIu, Evartau EE (1996) The effect of the NMDA-receptor antagonist (+/− )-CPP on the conditioned-reflex activation of an operant reaction in the brain electrical self-stimulation test in rats. Zh Vyssh Nerv Deiat Im I P Pavlova 46:117–121PubMedGoogle Scholar
  2. Bharne AP, Borkar CD, Subhedar NK, Kokare DM (2015) Differential expression of CART in feeding and reward circuits in binge eating rat model. Behav Brain Res 291:219–231CrossRefPubMedGoogle Scholar
  3. Carlezon WA Jr, Chartoff EH (2007) Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation. Nat Protoc 2:2987–2995CrossRefPubMedGoogle Scholar
  4. Choi DL, Davis JF, Magrisso IJ, Fitzgerald ME, Lipton JW, Benoit SC (2012) Orexin signaling in the paraventricular thalamic nucleus modulates mesolimbic dopamine and hedonic feeding in the rat. Neuroscience 210:243–248CrossRefPubMedPubMedCentralGoogle Scholar
  5. Cornwall J, Phillipson OT (1988) Afferent projections to the dorsal thalamus of the rat as shown by retrograde lectin transport. II. The midline nuclei. Brain Res Bull 21:147–161CrossRefPubMedGoogle Scholar
  6. Coulombe D, Miliaressis E (1987) Fitting intracranial self-stimulation data with growth models. Behav Neurosci 101:209–214CrossRefPubMedGoogle Scholar
  7. Dandekar MP, Singru PS, Kokare DM, Lechan RM, Thim L, Clausen JT, Subhedar NK (2008) Importance of cocaine- and amphetamine-regulated transcript peptide in the central nucleus of amygdala in anxiogenic responses induced by ethanol withdrawal. Neuropsychopharmacology 33:1127–1136CrossRefPubMedGoogle Scholar
  8. Dandekar MP, Singru PS, Kokare DM, Subhedar NK (2009) Cocaine- and amphetamine-regulated transcript peptide plays a role in the manifestation of depression: social isolation and olfactory bulbectomy models reveal unifying principles. Neuropsychopharmacology 34:1288–1300CrossRefPubMedGoogle Scholar
  9. Dayas CV, McGranahan TM, Martin-Fardon R, Weiss F (2008) Stimuli linked to ethanol availability activate hypothalamic CART and orexin neurons in a reinstatement model of relapse. Biol Psychiatry 63:152–157CrossRefPubMedGoogle Scholar
  10. den Hartog CR, Gilstrap M, Eaton B, Lench DH, Mulholland PJ, Homanics GE, Woodward JJ (2017) Effects of repeated ethanol exposures on NMDA receptor expression and locomotor sensitization in mice expressing ethanol resistant NMDA receptors. Front Neurosci 11:84CrossRefGoogle Scholar
  11. Desai SJ, Upadhya MA, Subhedar NK, Kokare DM (2013) NPY mediates reward activity of morphine, via NPY Y1 receptors, in the nucleus accumbens shell. Behav Brain Res 247:79–91CrossRefPubMedGoogle Scholar
  12. Desai SJ, Bharne AP, Upadhya MA, Somalwar AR, Subhedar NK, Kokare DM (2014) A simple and economical method of electrode fabrication for brain self-stimulation in rats. J Pharmacol Toxicol Methods 69:141–149CrossRefPubMedGoogle Scholar
  13. Deutch AY, Bubser M, Young CD (1998) Psychostimulant-induced Fos protein expression in the thalamic paraventricular nucleus. J Neurosci 18:10680–10687PubMedGoogle Scholar
  14. Elias CF, Lee CE, Kelly JF, Ahima RS, Kuhar M, Saper CB et al (2001) Characterization of CART neurons in the rat and human hypothalamus. J Comp Neurol 432:1–19CrossRefPubMedGoogle Scholar
  15. Fitzgerald LW, Ortiz J, Hamedani AG, Nestler EJ (1996) Drugs of abuse and stress increase the expression of GluR1 and NMDAR1 glutamate receptor subunits in the rat ventral tegmental area: common adaptations among cross-sensitizing agents. J Neurosci 16:274–282PubMedGoogle Scholar
  16. Frassoni C, Spreafico R, Bentivoglio M (1997) Glutamate, aspartate and co-localization with calbindin in the medial thalamus. An immunohistochemical study in the rat. Exp Brain Res 115:95–104CrossRefPubMedGoogle Scholar
  17. Fulton S, Woodside B, Shizgal P (2000) Modulation of brain reward circuitry by leptin. Science 287:125–128CrossRefPubMedGoogle Scholar
  18. Hamlin AS, Clemens KJ, Choi EA, McNally GP (2009) Paraventricular thalamus mediates context-induced reinstatement (renewal) of extinguished reward seeking. Eur J Neurosci 29:802–812CrossRefPubMedGoogle Scholar
  19. Herzog E, Bellenchi GC, Gras C, Bernard V, Ravassard P, Bedet C, Gasnier B, Giros B, El Mestikawy S (2001) The existence of a second vesicular glutamate transporter specifies subpopulations of glutamatergic neurons. J Neurosci 21:181Google Scholar
  20. Holahan MR, Westby EP, Albert K (2012) Comparison of the MK-801-induced appetitive extinction deficit with pressing for reward and associated pERK1/2 staining in prefrontal cortex and nucleus accumbens. Behav Brain Res 228:194–202CrossRefPubMedGoogle Scholar
  21. Huang H, Ghosh P, van den Pol AN (2006) Prefrontal cortex-projecting glutamatergic thalamic paraventricular nucleus-excited by hypocretin: a feedforward circuit that may enhance cognitive arousal. J Neurophysiol 95:1656–1668CrossRefPubMedGoogle Scholar
  22. James MH, Dayas CV (2013) What about me…? The PVT: a role for the paraventricular thalamus (PVT) in drug-seeking behavior. Front Behav Neurosci 7:18CrossRefPubMedPubMedCentralGoogle Scholar
  23. James MH, Charnley JL, Jones E, Levi EM, Yeoh JW, Flynn JR, Smith DW, Dayas CV (2010) Cocaine- and amphetamine-regulated transcript (CART) signaling within the paraventricular thalamus modulates cocaine-seeking behaviour. PLoS One 5:e12980CrossRefPubMedPubMedCentralGoogle Scholar
  24. James MH, Charnley JL, Levi EM, Jones E, Yeoh JW, Smith DW, Dayas CV (2011) Orexin-1 receptor signalling within the ventral tegmental area, but not the paraventricular thalamus, is critical to regulating cue-induced reinstatement of cocaine-seeking. Int J Neuropsychopharmacol 14:684–690CrossRefPubMedGoogle Scholar
  25. James MH, Yeoh JW, Graham BA, Dayas CV (2012) Insights for developing pharmacological treatments for psychostimulant relapse targeting hypothalamic peptide systems. J Addict Res Ther S 4:008Google Scholar
  26. James MH, Mahler SV, Moorman DE, Aston-Jones G (2017) A decade of orexin/hypocretin and addiction: where are we now? Curr Top Behav Neurosci 33:247–281CrossRefPubMedPubMedCentralGoogle Scholar
  27. Jaworski JN, Jones DC (2006) The role of CART in the reward/reinforcing properties of psychostimulants. Peptides 27:1993–2004CrossRefPubMedGoogle Scholar
  28. Jaworski JN, Kozel MA, Philpot KB, Kuhar MJ (2003) Intra-accumbal injection of CART (cocaine-amphetamine regulated transcript) peptide reduces cocaine-induced locomotor activity. J Pharmacol Exp Ther 307:1038–1044CrossRefPubMedGoogle Scholar
  29. Job MO, Kuhar MJ (2017) CART peptide in the nucleus accumbens regulates psychostimulants: correlations between psychostimulant and CART peptide effects. Neuroscience 348:135–142CrossRefPubMedGoogle Scholar
  30. Jones MW, Kilpatrick IC, Phillipson OT (1989) Regulation of dopamine function in the nucleus accumbens of the rat by the thalamic paraventricular nucleus and adjacent midline nuclei. Exp Brain Res 76:572–580CrossRefPubMedGoogle Scholar
  31. Kelley AE, Baldo BA, Pratt WE (2005) A proposed hypothalamic–thalamic–striatal axis for the integration of energy balance, arousal, and food reward. J Comp Neurol 493:72–85CrossRefPubMedGoogle Scholar
  32. Kimmel HL, Gong W, Vechia SD, Hunter RG, Kuhar MJ (2000) Intra-ventral tegmental area injection of rat cocaine- and amphetamine-regulated transcript peptide 55–102 induces locomotor activity and promotes conditioned place preference. J Pharmacol Exp Ther 294:784–792PubMedGoogle Scholar
  33. Kirouac GJ (2015) Placing the paraventricular nucleus of the thalamus within the brain circuits that control behavior. Neurosci Biobehav Rev 56:315–329CrossRefPubMedGoogle Scholar
  34. Kirouac GJ, Parsons MP, Li S (2005) Orexin (hypocretin) innervation of the paraventricular nucleus of the thalamus. Brain Res 1059:179–188CrossRefPubMedGoogle Scholar
  35. Kirouac GJ, Parsons MP, Li S (2006) Innervation of the paraventricular nucleus of the thalamus from cocaine- and amphetamine-regulated transcript (CART) containing neurons of the hypothalamus. J Comp Neurol 497:155–165CrossRefPubMedGoogle Scholar
  36. Kokare DM, Shelkar GP, Borkar CD, Nakhate KT, Subhedar NK (2011) A simple and inexpensive method to fabricate a cannula system for intracranial injections in rats and mice. J Pharmacol Toxicol Methods 64:246–250CrossRefPubMedGoogle Scholar
  37. Kolaj M, Zhang L, Hermes ML, Renaud LP (2014) Intrinsic properties and neuropharmacology of midline paraventricular thalamic nucleus neurons. Front Behav Neurosci 8:132CrossRefPubMedPubMedCentralGoogle Scholar
  38. Koylu EO, Couceyro PR, Lambert PD, Ling NC, DeSouza EB, Kuhar MJ (1997) Immunohistochemical localization of novel CART peptides in rat hypothalamus, pituitary and adrenal gland. J Neuroendocrinol 9:823–833CrossRefPubMedGoogle Scholar
  39. Kuhar MJ (2016) CART peptides and drugs of abuse: a review of recent progress. J Drug Alcohol Res.  https://doi.org/10.4303/jdar/235984 PubMedPubMedCentralGoogle Scholar
  40. Kuhar MJ, Jaworski JN, Hubert GW, Philpot KB, Dominguez G (2005) Cocaine- and amphetamine-regulated transcript peptides play a role in drug abuse and are potential therapeutic targets. AAPS J 7:E259–E265CrossRefPubMedPubMedCentralGoogle Scholar
  41. Lakatos A, Prinster S, Vicentic A, Hall RA, Kuhar MJ (2005) Cocaine- and amphetamine-regulated transcript (CART) peptide activates the extracellular signal-regulated kinase (ERK) pathway in AtT20 cells via putative G-protein coupled receptors. Neurosci Lett 384:198–202CrossRefPubMedGoogle Scholar
  42. Lee JS, Lee EY, Lee HS (2015) Hypothalamic, feeding/arousal-related peptidergic projections to the paraventricular thalamic nucleus in the rat. Brain Res 1598:97–113CrossRefPubMedGoogle Scholar
  43. Li S, Kirouac GJ (2008) Projections from the paraventricular nucleus of the thalamus to the forebrain, with special emphasis on the extended amygdala. J Comp Neurol 506:263–287CrossRefPubMedGoogle Scholar
  44. Li S, Kirouac GJ (2012) Sources of inputs to the anterior and posterior aspects of the paraventricular nucleus of the thalamus. Brain Struct Funct 217:257–273CrossRefPubMedGoogle Scholar
  45. Li Y, Li S, Wei C, Wang H, Sui N, Kirouac GJ (2010a) Changes in emotional behavior produced by orexin microinjections in the paraventricular nucleus of the thalamus. Pharmacol Biochem Behav 95:121–128CrossRefPubMedGoogle Scholar
  46. Li Y, Li S, Wei C, Wang H, Sui N, Kirouac GJ (2010b) Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats. Psychopharmacology 212:251–265CrossRefPubMedGoogle Scholar
  47. Lin Y, Hall RA, Kuhar MJ (2011) CART peptide stimulation of G protein-mediated signaling in differentiated PC12 cells: identification of PACAP 6–38 as a CART receptor antagonist. Neuropeptides 45:351–358CrossRefPubMedPubMedCentralGoogle Scholar
  48. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(− Delta Delta C(T)) method. Methods 25:402–408CrossRefPubMedGoogle Scholar
  49. Ma YY, Guo CY, Yu P, Lee DY, Han JS, Cui CL (2006) The role of NR2B containing NMDA receptor in place preference conditioned with morphine and natural reinforcers in rats. Exp Neurol 200:343–355CrossRefPubMedGoogle Scholar
  50. Matzeu A, Zamora-Martinez ER, Martin-Fardon R (2014) The paraventricular nucleus of the thalamus is recruited by both natural rewards and drugs of abuse: recent evidence of a pivotal role for orexin/hypocretin signaling in this thalamic nucleus in drug-seeking behavior. Front Behav Neurosci 8:117CrossRefPubMedPubMedCentralGoogle Scholar
  51. Matzeu A, Weiss F, Martin-Fardon R (2015) Transient inactivation of the posterior paraventricular nucleus of the thalamus blocks cocaine-seeking behavior. Neurosci Lett 608:34–39CrossRefPubMedPubMedCentralGoogle Scholar
  52. Matzeu A, Kerr TM, Weiss F, Martin-Fardon R (2016) Orexin-A/hypocretin-1 mediates cocaine-seeking behavior in the posterior paraventricular nucleus of the thalamus via orexin/hypocretin receptor-2. J Pharmacol Exp Ther 359:273–279CrossRefPubMedPubMedCentralGoogle Scholar
  53. Moga MM, Weis RP, Moore RY (1995) Efferent projections of the paraventricular thalamic nucleus in the rat. J Comp Neurol 359:221–238CrossRefPubMedGoogle Scholar
  54. Nakhate KT, Dandekar MP, Kokare DM, Subhedar NK (2009) Involvement of neuropeptide Y Y1 receptors in the acute, chronic and withdrawal effects of nicotine on feeding and body weight in rats. Eur J Pharmacol 609:78–87CrossRefPubMedGoogle Scholar
  55. Negus SS, Miller LL (2014) Intracranial self-stimulation to evaluate abuse potential of drugs. Pharmacol Rev 66:869–917CrossRefPubMedPubMedCentralGoogle Scholar
  56. Neumann PA, Wang Y, Yan Y, Wang Y, Ishikawa M, Cui R, Huang YH, Sesack SR, Schlüter OM, Dong Y (2016) Cocaine-induced synaptic alterations in thalamus to nucleus accumbens projection. Neuropsychopharmacology 41:2399–2410CrossRefPubMedPubMedCentralGoogle Scholar
  57. Otake K, Ruggiero DA, Nakamura Y (1995) Adrenergic innervation of forebrain neurons that project to the paraventricular thalamic nucleus in the rat. Brain Res 697:17–26CrossRefPubMedGoogle Scholar
  58. Parsons MP, Li S, Kirouac GJ (2006) The paraventricular nucleus of the thalamus as an interface between the orexin and CART peptides and the shell of the nucleus accumbens. Synapse 59:480–490CrossRefPubMedGoogle Scholar
  59. Parsons MP, Li S, Kirouac GJ (2007) Functional and anatomical connection between the paraventricular nucleus of the thalamus and dopamine fibers of the nucleus accumbens. J Comp Neurol 500:1050–1063CrossRefPubMedGoogle Scholar
  60. Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic Press, New YorkGoogle Scholar
  61. Philpot K, Smith Y (2006) CART peptide and the mesolimbic dopamine system. Peptides 27:1987–1992CrossRefPubMedGoogle Scholar
  62. Pinto A, Jankowski M, Sesack SR (2003) Projections from the paraventricular nucleus of the thalamus to the rat prefrontal cortex and nucleus accumbens shell: ultrastructural characteristics and spatial relationships with dopamine afferents. J Comp Neurol 459:142–155CrossRefPubMedGoogle Scholar
  63. Pitchers KK, Schmid S, Di Sebastiano AR, Wang X, Laviolette SR, Lehman MN, Coolen LM (2012) Natural reward experience alters AMPA and NMDA receptor distribution and function in the nucleus accumbens. PLoS One 7:e34700CrossRefPubMedPubMedCentralGoogle Scholar
  64. Rademacher DJ, Sullivan EM, Figge DA (2010) The effects of infusions of CART 55–102 into the basolateral amygdala on amphetamine-induced conditioned place preference in rats. Psychopharmacology 208:499–509CrossRefPubMedGoogle Scholar
  65. Sakharkar AJ, Zhang H, Tang L, Baxstrom K, Shi G, Moonat S, Pandey SC (2014) Effects of histone deacetylase inhibitors on amygdaloid histone acetylation and neuropeptide Y expression: a role in anxiety-like and alcohol-drinking behaviours. Int J Neuropsychopharmacol 17:1207–1220CrossRefPubMedPubMedCentralGoogle Scholar
  66. Schöne C, Cao ZF, Apergis-Schoute J, Adamantidis A, Sakurai T, Burdakov D (2012) Optogenetic probing of fast glutamatergic transmission from hypocretin/orexin to histamine neurons in situ. J Neurosci 32:12437–12443CrossRefPubMedGoogle Scholar
  67. Siahposht-Khachaki A, Fatahi Z, Haghparast A (2016) Reduction of the morphine maintenance by blockade of the NMDA receptors during extinction period in conditioned place preference paradigm of rats. Basic Clin Neurosci 7:341–350PubMedPubMedCentralGoogle Scholar
  68. Sikora M, Tokarski K, Bobula B, Zajdel J, Jastrzębska K, Cieślak PE, Zygmunt M, Sowa J, Smutek M, Kamińska K, Gołembiowska K, Engblom D, Hess G, Przewlocki R, Rodriguez Parkitna J (2016) NMDA receptors on dopaminoceptive neurons are essential for drug-induced conditioned place preference. eNeuro 3(3).  https://doi.org/10.1523/ENEURO.0084-15.2016
  69. Smith Y, Kieval J, Couceyro PR, Kuhar MJ (1999) CART peptide immunoreactive neurones in the nucleus accumbens in monkeys: ultrastructural analysis, colocalization studies, and synaptic interactions with dopaminergic afferents. J Comp Neurol 407:491–511CrossRefPubMedGoogle Scholar
  70. Smith-Roe SL, Kelley AE (2000) Coincident activation of NMDA and dopamine D1 receptors within the nucleus accumbens core is required for appetitive instrumental learning. J Neurosci 20:7737–7742PubMedGoogle Scholar
  71. Somalwar AR, Shelkar GP, Subhedar NK, Kokare DM (2017) The role of neuropeptide CART in the lateral hypothalamic-ventral tegmental area (LH–VTA) circuit in motivation. Behav Brain Res 317:340–349CrossRefPubMedGoogle Scholar
  72. Thompson RH, Swanson LW (2003) Structural characterization of a hypothalamic visceromotor pattern generator network. Brain Res Brain Res Rev 41:153–202CrossRefPubMedGoogle Scholar
  73. Tomasiewicz HC, Todtenkopf MS, Chartoff EH, Cohen BM, Carlezon WA Jr (2008) The kappa-opioid agonist U69,593 blocks cocaine-induced enhancement of brain stimulation reward. Biol Psychiatry 64:982–988CrossRefPubMedPubMedCentralGoogle Scholar
  74. Upadhya MA, Nakhate KT, Kokare DM, Singh U, Singru PS, Subhedar NK (2012) CART peptide in the nucleus accumbens shell acts downstream to dopamine and mediates the reward and reinforcement actions of morphine. Neuropharmacology 62:1823–1833CrossRefPubMedGoogle Scholar
  75. Van der Werf YD, Witter MP, Groenewegen HJ (2002) The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness. Brain Res Brain Res Rev 39:107–140CrossRefPubMedGoogle Scholar
  76. Vertes RP, Hoover WB (2008) Projections of the paraventricular and paratenial nuclei of the dorsal midline thalamus in the rat. J Comp Neurol 508:212–237CrossRefPubMedGoogle Scholar
  77. Vrang N, Larsen PJ, Clausen JT, Kristensen P (1999) Neurochemical characterization of hypothalamic cocaine-amphetamine-regulated transcript neurons. J Neurosci 19:RC5PubMedGoogle Scholar
  78. Walker LC, Lawrence AJ (2017) The role of orexins/hypocretins in alcohol use and abuse. Curr Top Behav Neurosci 33:221–246CrossRefPubMedGoogle Scholar
  79. Wise RA (1996) Addictive drugs and brain stimulation reward. Annu Rev Neurosci 19:319–340CrossRefPubMedGoogle Scholar
  80. Wolf ME (2010) Regulation of AMPA receptor trafficking in the nucleus accumbens by dopamine and cocaine. Neurotox Res 18:393–409CrossRefPubMedPubMedCentralGoogle Scholar
  81. Yang SC, Pan JT, Li HY (2004) CART peptide increases the mesolimbic dopaminergic neuronal activity: a microdialysis study. Eur J Pharmacol 494:179–182CrossRefPubMedGoogle Scholar
  82. Yeoh JW, James MH, Graham BA, Dayas CV (2014) Electrophysiological characteristics of paraventricular thalamic (PVT) neurons in response to cocaine and cocaine- and amphetamine-regulated transcript (CART). Front Behav Neurosci 8:280CrossRefPubMedPubMedCentralGoogle Scholar
  83. Yermolaieva O, Chen J, Couceyro PR, Hoshi T (2001) Cocaine- and amphetamine-regulated transcript peptide modulation of voltage-gated Ca2+ signaling in hippocampal neurons. J Neurosci 21:7474–7480PubMedGoogle Scholar
  84. Young CD, Deutch AY (1998) The effects of thalamic paraventricular nucleus lesions on cocaine-induced locomotor activity and sensitization. Pharmacol Biochem Behav 60:753–758CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Amit G. Choudhary
    • 1
  • Amita R. Somalwar
    • 1
  • Sneha Sagarkar
    • 2
  • Abhishek Rale
    • 3
  • Amul Sakharkar
    • 2
  • Nishikant K. Subhedar
    • 3
  • Dadasaheb M. Kokare
    • 1
  1. 1.Department of Pharmaceutical SciencesRashtrasant Tukadoji Maharaj Nagpur UniversityNagpurIndia
  2. 2.Department of BiotechnologySavitribai Phule Pune UniversityPuneIndia
  3. 3.Indian Institute of Science Education and Research (IISER)PuneIndia

Personalised recommendations