Skip to main content
Log in

Differential behavioral effects following microinjection of an NMDA antagonist into nucleus accumbens subregions

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Recent studies have demonstrated the existence of two distinct regions within the nucleus accumbens (N.Acc) known as “core” and “shell”. In order to investigate whether the behavioral functions of excitatory amino acid receptors differed between these two subregions, rats were administered microinjections of 2-amino-5-phosphonovaleric acid (AP-5), a competitive NMDA antagonist (0, 0.05, 0.2, 0.5, 1.0 µg/0.5 µl) into selected central and medial regions of the accumbens. The central and medial sites were assumed to correspond approximately to core and shell subregions, respectively. The animals were tested in two exploratory tasks: the open field and a novel object test. In the open field test, AP-5 significantly decreased peripheral locomotion and center rearing frequency in the central but not the medial group. Locomotion and rearing were not affected by AP5 infusion into a control site, the anterior dorsal striatum (ADS). In the novel object test, animals were tested in the same open field, with prior habituation, and with several novel objects placed within it. In this test, infusions of AP-5 (0, 1.0 µg/0.5 µl) decreased the number and duration of contacts with the novel objects in the central but not the medial group. In addition, peripheral and center locomotion were decreased by AP-5 infusions into the central site, whether objects were present or not. In contrast, AP-5 infusions into the medial site elicited an increase in peripheral locomotion in both stimulus conditions. These findings provide behavioral-pharmacological evidence that the central and medial subregions of the nucleus accumbens can be differentiated. Moreover, the results suggest that exploratory motor responses may be dependent on glutamate-coded input to the nucleus accumbens area corresponding to the core region.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albin RL, Makowiec RL, Hollingsworth ZR, Dure IV LS, Penney JB, Young AB (1991) Excitatory amino acid binding sites in the basal ganglia of the rat: a quantitative autoradiographic study. Neuroscience 46:35–48

    Google Scholar 

  • Alheid GF, Heimer L (1988) New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders; striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience 27:1–39

    Google Scholar 

  • Bakshi VP, Kelley AE (1991) Dopaminergic regulation of feeding behavior: Differential effects of haloperidol infusion into three striatal subregions. Psychobiology 19[3]:223–232

    Google Scholar 

  • Berendse HW, Groenewegen HJ, Lohman AHM (1992) Compartmental distribution of ventral striatal neurons projecting to the mesencephalon in the rat. J Neurosci 12:2079–2103

    Google Scholar 

  • Bouyer JJ, Park DH, Joh TH, Pickel VM (1984) Chemical and structural analysis of the relation between cortical inputs and tyrosine hydroxylase-containing terminals in the rat neostriatum. Brain Res 302:267–275

    Google Scholar 

  • Brog JS, Deutch AY, Zahm DS (1991) Afferent projections to the nucleus accumbens core and shell in the rat. Soc Neurosci Abstr 17:454

    Google Scholar 

  • Burns LH, Everitt BJ, Robbins TW (1991) Functional interactions of limbic afferents to the ventral striatum with mesolimbic dopamine: studies of conditioned reinforcement and locomotor activity in the rat. Soc Neurosci Abstr 17:1249

    Google Scholar 

  • Cheramy A, Romo R, Godeheu G, Baruch P, Glowinski J (1986) In vivo presynaptic control of dopamine release in the cat caudate nucleus: II. Facilitatory or inhibitory influence ofl-glutamate. Neuroscience 19:1081–1090

    Google Scholar 

  • Dawbarn D, Pycock CJ (1981) Motor effects following application of putative excitatory amino acid antagonists to the region of the mesencephalic dopamine cell bodies in the rat. Naunyn-Schmiedeberg's Arch Pharmacol 318:100–104

    Google Scholar 

  • Deutch AY, Cameron DS (1991) Pharmacological characterization of dopamine systems in the nucleus accumbens core and shell. Neuroscience 46:49–56

    Google Scholar 

  • Donzanti BA, Uretsky NJ (1983) Effects of excitatory amino acids on locomotor activity after bilateral microinjection into the rat nucleus accumbens: possible dependence on dopaminergic mechanisms. Neuropharmacology 22:971–981

    Google Scholar 

  • Douglas RJ, Isaacson RL (1964) Hippocampal lesions and activity. Psychon Sci 1:187–188

    Google Scholar 

  • Falls WA, Miserindino MJD, Davis M (1992) Extinction of fearpotentiated startle: blockade by infusion of an NMDA antagonist into the amygdala. J Neurosci 12:854–863

    Google Scholar 

  • Freund TF, Powell JF, Smith AD (1984) Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines. Neuroscience 13:1189–1216

    Google Scholar 

  • Fuller TA, Russchen FT, Price JLP (1987) Sources of presumptive glutamergic/apartergic afferents to the rat ventral striatopallidal region. J Comp Neurol 258:317–338

    Google Scholar 

  • Girault JA, Barbeito L, Spampinato U, Gozlan H, Glowinski J, Besson MJ (1986) In vivo release of endogenous amino acids from the rat striatum: further evidence for a role of glutamate and aspartate in corticostriatal neurotransmission. J Neurochem 47:98–106

    Google Scholar 

  • Groenewegen HJ, Vermeulen-Van der Zee E, te Kortschot A, Witter MP (1987) Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of phaseolus vulgaris leucoagglutinin. Neuroscience 23:103–120

    Google Scholar 

  • Hannigan JH, Springer JE, Isaacson RL (1984) Differentiation of basal ganglia dopaminergic involvement in behavior after hippocampectomy. Brain Res 291:83–125

    Google Scholar 

  • Hassler R, Haug P, Nitsch C, Kim JS, Paik K (1982) Effect of motor and premotor cortex ablation on concentrations of amino acids, monamines, and acetylcholine and on the ultrastructure in rat striatum. A confirmation of glutamate as the specific cortico-striatal transmitter. J Neurochem 38:1087–1098

    Google Scholar 

  • Heimer L, Zahm DS, Churchill L, Kalivas PW, Wohltmann C (1991) Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience 41:89–125

    Google Scholar 

  • Kelley AE, Stinus L (1985) Disappearance of hoarding behavior after 6-hydroxydopamine lesions of the mesolimbic dopamine neurons and its reinstatement withl-dopa. Behav Neurosci 99:531–545

    Google Scholar 

  • Kelley AE, Throne LC (1992) NMDA receptors mediate the behavioral effects of amphetamine infused into the nucleus accumbens. Brain Res Bull 29:247–254

    Google Scholar 

  • Kimble DP (1968) Hippocampus and internal inhibition. Psychol Bull 70:285–295

    Google Scholar 

  • Kita H, Kitai ST (1990) Amygdaloid projections to the frontal cortex and the striatum in the rat. J Comp Neurol 298:40–49

    Google Scholar 

  • Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242:715–723

    Google Scholar 

  • Koob GF, Stinus L, Le Moal M (1981) Hyperactivity and hypoactivity produced by lesions to the mesolimbic dopamine system. Behav Brain Res 3:341–359

    Google Scholar 

  • McDonald AJ (1991a) Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the rat. Neuroscience 44:1–14

    Google Scholar 

  • McDonald AJ (1991b) Topographical organization of amygdaloid projections to the caudotoputamen, nucleus accumbens, and related striatal-like areas of the rat brain. Neuroscience 44:15–33

    Google Scholar 

  • McGeer PL, McGeer EG, Scherer U, Singh K (1977) A glutamatergic corticostriatal pathway? Brain Res 128:369–373

    Google Scholar 

  • McGeorge AJ, Faull RLM (1989) The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience 29:503–537

    Google Scholar 

  • Meredith GE, Agolia R, Arts MPM, Groenewegen HJ, Zahm DS (1992) Morphological differences between projections neurons of the core and shell in the nucleus accumbens of the rat. Neuroscience 50:149–162

    Google Scholar 

  • Mogenson GJ, Nielsen M (1984a) A study of the contribution of hippocampal-accumbens-subpallidal projections to locomotor activity. Behav Neural Biol 42:38–51

    Google Scholar 

  • Mogenson GJ, Nielsen M (1984b) Neuropharmacological evidence to suggest that the nucleus accumbens and subpallidal region contribute to exploratory locomotion. Behav Neural Biol 42:52–60

    Google Scholar 

  • Mogenson GJ, Jones DL, Yim CY (1980) From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 14:69–97

    Google Scholar 

  • Mount H, Welner S, Quirion R (1989) Glutamate stimulation of [3H] dopamine release form dissociated cell cultures of rat ventral mesencephalon. J Neurochem 52:1300–1310

    Google Scholar 

  • Pennartz CMA, Boeijinga PH, Lopes da Silva FH (1990) Locally evoked potentials in slices of the rat nucleus accumbens: NMDA and non-NMDA receptor mediated components and modulation by GABA. Brain Res 529:30–41

    Google Scholar 

  • Pennartz CMA, Dolleman-Van der Weel MJ, Lopes da Silva FH (1992) Differential membrane properties and dopamine effects in the shell and core of the rat nucleus accumbens studied in vitro. Neurosci Lett 136:109–112

    Google Scholar 

  • Pulvirenti L, Swerdlow NR, Koob GF (1989) Microinjection of a glutamate antagonist into the nucleus accumbens reduces psychostimulant locomotion in rats. Neurosci Lett 103:213–218

    Google Scholar 

  • Pulvirenti L, Swerdlow NR, Koob GF (1991) Nucleus accumbens NMDA antagonist decreases locomotor activity produced by cocaine, heroin or accumbens dopamine, but not caffeine. Pharmacol Biochem Behav 40:841–845

    Google Scholar 

  • Robbins TW, Cador M, Taylor JR, Everitt BJ (1989) Limbic-striatal interactions in reward-related processes. Neurosci Biobehav Rev 13:155–162

    Google Scholar 

  • Roberts PJ, Sharif NA (1978) Effects ofl-glutamate and related amino acids upon the release of3H-dopamine from rat striatal slices. Brain Res 157:391–395

    Google Scholar 

  • Robinson TG, Beart PM (1988) Excitant amino acid projections from rat amygdala and thalamus to nucleus accumbens. Brain Res Bull 20:467–471

    Google Scholar 

  • Save E, Poucet B, Foreman N, Buhot M-C (1992) Object exploration and reactions to spatial and nonspatial changes in hooded rats following damage to parietal cortex or hippocampal formation. Behav Neurosci 106:447–456

    Google Scholar 

  • Sesack SR, Pickel VM (1990) In the rat nucleus accumbens, hippocampal and catecholaminergic terminals converge on spiny neurons and are in apposition to each other. Brain Res 527:266–279

    Google Scholar 

  • Shimizu N, Duan S, Hori T, Oomura Y (1990) Glutamate modulates dopamine release in the striatum as measured by brain microdialysis. Brain Res Bull 25:99–102

    Google Scholar 

  • Smith AD, Bolam JP (1990) The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones. Trends Neurosci 13:259–265

    Google Scholar 

  • Somogyi P, Bolam JP, Smith AD (1981) Monosynaptic cortical input and local axon collaterals of identified stratonigral neurons. A light and electron microscopic study using the Golgiperoxidase transport-degeneration procedure. J Comp Neurol 195:567–584

    Google Scholar 

  • Tallaksen-Greene SJ, Wiley RG, Albin RL (1992) Localization of striatal excitatory amino acid binding site subtypes to striatonigral projection neurons. Brain Res 594:165–170

    Google Scholar 

  • Voorn P, Gerfen CR, Groenewegen HJ (1989) Compartmental organization of the ventral striatum of the rat: immunohistochemical distribution of enkephalin, substance P, dopamine, and calcium-binding protein. J Comp Neurol 289:189–201

    Google Scholar 

  • Walaas I, Fonnum F (1979) The effects of surgical and chemical lesions on neurotransmitter candidates on the nucleus accumbens. Neuroscience 4:209–216

    Google Scholar 

  • Yang CR, Mogenson GJ (1984) Electrophysiological responses of neurones in the nucleus accumbens to hippocampal stimulation and the attenuation of the excitatory responses by the mesolimbic dopaminergic system. Brain Res 324:69–84

    Google Scholar 

  • Zaborszky L, Alheid GF, Beinfeld MC, Eiden LE, Heimer L, Palkovits M (1985) Cholecystokinin innervation of the ventral striatum: a morphological and radioimmunological study. Neuroscience 14:427–453

    Google Scholar 

  • Zahm DS, Brog JS (1992) On the significance of subterritories in the “accumbens” part of the rat ventral striatum. Neuroscience 50:751–767

    Google Scholar 

  • Zahm DS, Heimer L (1990) Two transpallidal pathways originating in rat nucleus accumbens. J Comp Neurol 302:437–446

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maldonado-Irizarry, C.S., Kelley, A.E. Differential behavioral effects following microinjection of an NMDA antagonist into nucleus accumbens subregions. Psychopharmacology 116, 65–72 (1994). https://doi.org/10.1007/BF02244872

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02244872

Key words

Navigation