Abstract
Previous evidence suggests that glutamatergic limbic afferents participate in the potentiation of responding with conditioned reinforcement produced by intra-accumbens d-amphetamine. The present experiments were designed to investigate glutamate-dopamine interactions in the ventral striatum in both conditioned reinforcement and locomotor activity. Glutamate receptor agonists and antagonists were infused into the nucleus accumbens both alone and in combination with 3 µg d-amphetamine, and the effects of these interactions on responding with conditioned reinforcement and locomotor activity were measured. The glutamate receptor agonists NMDA, AMPA and quisqualate (agonists at the NMDA, AMPA and metabotropic glutamate receptor subtypes, respectively) and the antagonists AP5 and CNQX, (antagonists at the NMDA and AMPA receptor subtypes, respectively) were used in these investigations. These compounds were used in a dose range of 0.3 to 3 nmol, except CNQX, which was used in 0.2 to 2 nmol doses. While all agonists and antagonists increased locomotor activity when administered alone, the antagonists attenuated the locomotor response to d-amphetamine. In contrast, the agonists AMPA and quisqualate enhanced d-amphetamine-induced locomotor activity, although NMDA interfered with the effects of d-amphetamine. In the conditioned reinforcement paradigm, both the agonists and the antagonists abolished amphetamine's potentiation of responding with conditioned reinforcement, suggesting that the glutamatergic transmission of information about the conditioned reinforcer could be blocked by glutamate receptor antagonists and disrupted by administration of the agonists. The dissociation between the effects of these excitatory amino acids on amphetamine-induced locomotor activity versus their effects on amphetamine's potentiation of responding with conditioned reinforcement provides insight into the nature of the reward enhancement by accumbens dopamine versus its locomotor stimulant effects.
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References
Arnt J (1981) Hyperactivity following injection of a glutamate agonist and 6,7-ADTN into rat nucleus accumbens and its inhibition by THIP. Life Sci 28: 1597–1603.
Beninger RJ (1991) D1 receptor involvement in reward-related learning. J Psychopharmacol 6: 34–42.
Boldry RC, Uretsky NJ (1988) The importance of dopaminergic neurotransmission in the hypermotility response produced by the administration of N-methyl-d-aspartic acid into the nucleus accumbens. Neuropharmacology 27: 569–577.
Boldry RC, Willins DL, Wallace LJ, Uretsky NJ (1991) The role of endogenous dopamine in the hypermotility response to intra-accumbens AMPA. Brain Res 559: 100–108.
Burns LH, Robbins TW, Everitt BJ (1993) Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of d-amphetamine. Behav Brain Res 55: 167–183.
Cador M, Robbins TW, Everitt BJ (1989) Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum. Neuroscience 30: 77–86.
Cador M, Taylor JR, Robbins TW (1991) Potentiation of the effects of reward-related stimuli by dopaminergic mechanisms in the nucleus accumbens. Psychopharmacology 104: 377–385.
Carrozza DP, Ferraro TN, Golden GT, Reyes PF, Hare TA (1992) In vivo modulation of excitatory amino acid receptors: microdialysis studies on N-methyl-D-aspartate-evoked striatal dopamine release and effects of antagonists. Brain Res 574: 42–48.
Chéramy A, Romo R, Bodeheu G, Baruch P, Glowinski J (1986) In vivo presynaptic control of dopamine release in the cat caudate nucleus — II. Facilitatory of inhibitory influence of L-glutamate. Neuroscience 19(4):1081–1090.
Christie MJ, Summers RJ, Stephenson JA, Cook CJ, Beart PM (1987) Excitatory amino acid projections to the nucleus accumbens septi in the rat: a retrograde transport study utilizing D[3H]aspartate and [3H]GABA. Neuroscience 22: 425–439.
Chu B, Kelley AE (1992) Potentiation of reward-related responding by psychostimulant infusion into nucleus accumbens: Role of dopamine receptor subtypes. Psychobiology 20: 153–162.
Cools AR, Peters BWMM (1987) Behavioral function of neostriatal glutamate and its interaction with dopamine. Neurosci Res Comm 1(1):47–55.
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.
Fuller TA, Russchen FT, Price JL (1987) Sources of presumptive glutamergic/aspartergic afferents to the ventral striatopallidal region. J Comp Neurol 258: 317–338.
Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41(1):1–24.
Greenamyre JT, Young AB (1989) Synaptic localization of striatal NMDA, quisqualate and kainate receptors. Neurosci Lett 101: 133–137.
Herberg LJ, Rose IC (1989) The effect of MK-801 and other antagonists of NMDA-type glutamate receptors on brain-stimulation reward. Psychopharmacology 99: 87–90.
Hamilton MH, De Belleroche JS, Gardiner IM, Herberg LJ (1986) Stimulatory effect of N-methyl aspartate on locomotor activity and transmitter release from rat nucleus accumbens. Pharmacol Biochem Behav 25: 943–948.
Honoré T, Davies SN, Dreger J, Fletcher EJ, Jacobsen P, Lodge D, Nielsen FE (1988) Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. Science 241: 701–703.
Imperato A, Honoré T, Jensen LH (1990) Dopamine release in the nucleus caudatus and in the nucleus accumbens is under glutamatergic control through non-NMDA receptors: A study in freely-moving rats. Brain Res 530: 223–228.
Kelley AE, Delfs JM (1991) Dopamine and conditioned reinforcement. Differential effects of amphetamine microinjections into striatal subregions. Psychopharmacology 103: 187–196.
Kelley AE, Throne LC (1992) NMDA receptors mediate the behavioral effects of amphetamine infused into the nucleus accumbens. Brain Res Bull 29: 247–254.
Koek W, Colpaert FC (1990) Selective blockade of N-methyl-d-aspartate-(NMDA-) induced convulsions by NMDA antagonists and putative glycine antagonists: relations with phenylcyclidine-like behavioral effects. J Pharm Exp Ther 252: 349–374.
Leviel V, Borbert A, Buibert B (1990) The glutamate-mediated release of dopamine in the rat striatum: Further characterization of the dual excitatory-inhibitory function. Neuroscience 39(2):305–312.
Mackintosh NJ (1974) The Psychology of Animal Learning. Academic Press, London.
Mercuri N, Bernardi G, Calabresi P, Cotugno A, Levi G, Stanzione P (1985) Dopamine decreases cell excitability in rat striatal neurons by pre- and postsynaptic mechanisms. Brain Res 358(1–2):110–121.
Moghaddam B, Gruen RJ, Roth RH, Bunney BS, Adams RN (1990) Effect of L-glutamate on the release of striatal dopamine: in vivo dialysis and electrochemical studies. Brain Res 518: 55–60.
Pennartz CMA (1992) Chapter 9 in Electrophysiology of the rat nucleus accumbens. Local circuitry, neuromodulation and synaptic plasticity. Thesis, Dept of Expt Zoology, University of Amsterdam.
Pennartz CMA, Boeijinga PH, Kitai ST, Lopes de Silva FH (1991) Contribution of NMDA receptors to postsynaptic potentials and paired-pulse facilitation in identified neurons of the rat nucleus accumbens in vitro. Exp Brain Res 86: 190–198.
Pennartz CMA, Boeijinga PH, Lopes de 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.
Pennartz CMA, Kitai ST (1991) Hippocampal inputs to identified neurons in an in vitro slice preparation of the rat nucleus accumbens: Evidence for feed-forward inhibition. J Neurosci 11(9):2838–2847.
Pijnenburg AJJ, Honig WM, Van der Heyden JAM, Van Rossum JM (1975) Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Eur J Pharmacol 35: 49–58.
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(4):841–845.
Robbins TW (1976) Relationship between reward-enhancing and stereotypical effects of psychomotor stimulant drugs. Nature 264: 57–59.
Robbins TW (1978) The acquisition of responding with conditioned reinforcement: effects of pipradol, methylphenidate, d-amphetamine, and nomifensine. Psychopharmacology 58(1): 79–87.
Sesack SR, Pickel VM (1990) In the rat medial nucleus accumbens, hippocampal and catecholaminergic terminals converge on spiny neurons and are in apposition to each other. Brain Res 527(2):83–91.
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.
Shreve PE, Uretsky NJ (1988) Role of quisqualic acid receptors in the hypermotility response produced by the injection of AMPA into the nucleus accumbens. Pharmacol Biochem Behav 30: 379–384.
Smith AD, Bolam JP (1990) The neuronal network of the basal ganglia as revealed by the study of synaptic connections of identified neurones. TINS 13: 259–265.
Taylor JR, Robbins TW (1984) Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology 84: 405–412.
Taylor JR, Robbins TW (1986) 6-Hydroxydopamine lesions of the nucleus accumbens, but not of the caudate nucleus, attenuate enhanced responding with reward-related stimuli produced by intra-accumbens d-amphetamine. Psychopharmacology 90: 390–397.
Tsai CT, Mogenson GJ, Wu M, Yang CR (1989) A comparison of the effects of electrical stimulation of the amygdala and hippocampus on subpallidal output neurons to the pedunculopontine nucleus. Brain Res 494: 22–29.
Turski L, Meldrum BS, Cavalheiro EA, Calderazzo-Filho LS, Bortolotto ZA, Ikonomidou-Turski CKE, Turski WA (1987) Paradoxical anticonvulsant action of the excitatory amino-acid N-methyl-D-aspartate in the rat caudate-putamen. Proc Nat Acad Sci (U.S.A.) 84: 1689–1693.
Walaas I, Fonnum F (1980) Biochemical evidence for glutamate as a transmitter in hippocampal efferents to the basal forebrain and hypothalamus in the rat brain. Neuroscience 5: 1691–1698.
Watkins JC, Krogsgaard-Larsen P, Honoré T (1991) Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. TiPS Special Report: 4–12.
Wolterink G, Phillips G, Cador M, Donselaar-Wolterink I, Robbins TW, Everitt BJ (1993) Relative roles of ventral striatal D1 and D2 dopamine receptors in responding with conditioned reinforcement. Psychopharmacology 110: 355–364.
Winer BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York.
Yang CR, Mogenson GJ (1987) Hippocampal signal transmission to the pedunculopontine nucleus and its regulation by dopamine D2 receptors in the nucleus accumbens: an electrophysiological behavioural study. Neuroscience 23: 1041–1055.
Yim CY, Mogenson GJ (1989) Low doses of accumbens dopamine modulate amygdala suppression of spontaneous exploratory activity in rats. Brain Res 477: 202–210.
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Burns, L.H., Everitt, B.J., Kelley, A.E. et al. Glutamate-dopamine interactions in the ventral striatum: role in locomotor activity and responding with conditioned reinforcement. Psychopharmacology 115, 516–528 (1994). https://doi.org/10.1007/BF02245576
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DOI: https://doi.org/10.1007/BF02245576