Striatal dopamine in motor activation and reward-mediated learning: steps towards a unifying model

On the basis of behavioural evidence, dopamine is found to be involved in two higher-level functions of the brain: reward-mediated learning and motor activation. In these functions dopamine appears to mediate synaptic enhancement in the corticostriatal pathway. However, in electrophysiological studies, dopamine is often reported to inhibit corticostriatal transmission. These two effects of dopamine seem incompatible. The existence of separate populations of dopamine receptors, differentially modulating cholinergic and glutamatergic synapses, suggests a possible resolution to this paradox. The synaptic enhancement which occurs in reward-mediated learning may also be involved in dopamine-mediated motor activation. The logical form of reward-mediated learning imposes constraints on which mechanisms can be considered possible. Dopamine D1 receptors may mediate enhancement of corticostriatal synapses. On the other hand, dopamine D2 receptors on cholinergic terminals may mediate indirect, inhibitory effects of dopamine on striatal neurons.

[1]  M. Difiglia Synaptic organization of cholinergic neurons in the monkey neostriatum , 1987, The Journal of comparative neurology.

[2]  J. C. Stoof,et al.  Stimulation of D2-dopamine receptors in rat neostriatum inhibits the release of acetylcholine and dopamine but does not affect the release of gamma-aminobutyric acid, glutamate or serotonin. , 1982, European journal of pharmacology.

[3]  J. Walters,et al.  Effects of D1 and D2 dopamine receptor stimulation on the activity of substantia nigra pars reticulata neurons in 6-hydroxydopamine lesioned rats: D1/D2 coactivation induces potentiated responses , 1987, Brain Research.

[4]  H. Dodt,et al.  Muscarinic slow excitation and muscarinic inhibition of synaptic transmission in the rat neostriatum. , 1986, The Journal of physiology.

[5]  R. Wise,et al.  Pimozide attenuates lever pressing for water reinforcement in rats , 1981, Pharmacology Biochemistry and Behavior.

[6]  A. Björklund,et al.  Nigral transplants reinnervating the dopamine-depleted neostriatum can sustain intracranial self-stimulation. , 1983, Science.

[7]  J. Wu,et al.  Glutamate decarboxylase-like immunoreactive eurons in the rat caudate putamen , 1987, Brain Research Bulletin.

[8]  G. Wooten,et al.  Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  T. Dawson,et al.  Dopamine D-2 auto- and postsynaptic receptors in the nigrostriatal system of the rat brain: localization by quantitative autoradiography with [3H]sulpiride. , 1987, European journal of pharmacology.

[10]  P. Greengard,et al.  Dopaminergic regulation of protein phosphorylation in the striatum: DARPP-32 , 1987, Trends in Neurosciences.

[11]  Robert Miller Meaning and Purpose in the Intact Brain , 1981 .

[12]  W. Schultz,et al.  Responses of rat pallidum cells to cortex stimulation and effects of altered dopaminergic activity , 1985, Neuroscience.

[13]  Richard S. Sutton,et al.  Associative search network: A reinforcement learning associative memory , 1981, Biological Cybernetics.

[14]  J. Larsen,et al.  Pharmacological effects of a specific dopamine D-1 antagonist SCH 23390 in comparison with neuroleptics. , 1984, Life sciences.

[15]  A. Björklund,et al.  Striatal grafts in rats with unilateral neostriatal lesions—II. In vivo monitoring of gaba release in globus pallidus and substantia nigra , 1988, Neuroscience.

[16]  J. C. Stoof,et al.  Two dopamine receptors: biochemistry, physiology and pharmacology. , 1984, Life sciences.

[17]  A. Phillips,et al.  Dopaminergic substrates of intracranial self-stimulation in the caudate-putamen , 1976, Brain Research.

[18]  H. Szechtman Peripheral sensory input directs apomorphine-induced circling in rats , 1983, Brain Research.

[19]  R. Wise,et al.  Major attenuation of food reward with performance-sparing doses of pimozide in the rat. , 1978, Canadian journal of psychology.

[20]  Akinori Akaike,et al.  Excitatory and inhibitory effects of dopamine on neuronal activity of the caudate nucleus neurons in vitro , 1987, Brain Research.

[21]  T. Shippenberg,et al.  Place preference conditioning reveals the involvement of D1-dopamine receptors in the motivational properties of μ- and κ-opioid agonists , 1987, Brain Research.

[22]  G. Wooten,et al.  Localization of D-2 dopamine receptors to intrinsic striatal neurones by quantitative autoradiography , 1986, Nature.

[23]  J. Wickens Electrically coupled but chemically isolated synapses: Dendritic spines and calcium in a rule for synaptic modification , 1988, Progress in Neurobiology.

[24]  J. C. Stoof,et al.  Stimulation of D2-receptors in rat nucleus accumbens slices inhibits dopamine and acetylcholine release but not cyclic AMP formation , 1987, Brain Research.

[25]  P. Calabresi,et al.  Intracellular studies on the dopamine-induced firing inhibition of neostriatal neurons in vitro: Evidence for D1 receptor involvement , 1987, Neuroscience.

[26]  A. Gjedde,et al.  Does deoxyglucose uptake in the brain reflect energy metabolism? , 1987, Biochemical pharmacology.

[27]  E. T. Rolls,et al.  Responses of striatal neurons in the behaving monkey. 3. Effects of iontophoretically applied dopamine on normal responsiveness , 1984, Neuroscience.

[28]  J. Deniau,et al.  Disinhibition as a basic process in the expression of striatal functions , 1990, Trends in Neurosciences.

[29]  S. Nakajima Suppression of operant responding in the rat by dopamine D1 receptor blockade with SCH 23390 , 1986 .

[30]  J. Bouyer,et al.  Chemical and structural analysis of the relation between cortical inputs and tyrosine hydroxylase-containing terminals in rat neostriatum , 1984, Brain Research.

[31]  P. Groves,et al.  Three-dimensional structure of dendritic spines in the rat neostriatum , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  J. Walters,et al.  Single unit responses of substantia nigra pars reticula neurons to apomorphine: Effects of striatal lesions and anesthesia , 1984, Brain Research.

[33]  A. Björklund,et al.  Striatal grafts in rats with unilateral neostriatal lesions—III. Recovery from dopamine-dependent motor asymmetry and deficits in skilled paw reaching , 1988, Neuroscience.

[34]  Edward L. White,et al.  Dendritic spines are susceptible to structural alterations induced by degeneration of their presynaptic afferents , 1988, Brain Research.

[35]  L. Dwoskin,et al.  Biphasic modulation of evoked [3H]D‐aspartate release by D‐2 dopamine receptors in rat striatal slices , 1988, Synapse.

[36]  A. Randrup,et al.  Cholinergic mechanism in brain inhibiting amphetamine-induced stereotyped behaviour. , 2009, Acta pharmacologica et toxicologica.

[37]  J. Bolam,et al.  Cholinergic synaptic input to different parts of spiny striatonigral neurons in the rat , 1988, The Journal of comparative neurology.

[38]  G. Wooten,et al.  The effects ofl-DOPA on regional cerebral glucose utilization in rats with unilateral lesions of the substantia nigra , 1986, Brain Research.

[39]  James L Olds,et al.  Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. , 1954, Journal of comparative and physiological psychology.

[40]  U. Ungerstedt Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. , 1971, Acta physiologica Scandinavica. Supplementum.

[41]  J. Joyce,et al.  Quantitative autoradiography of dopamine D2 sites in rat caudate-putamen: Localization to intrinsic neurons and not to neocortical afferents , 1987, Neuroscience.

[42]  H. Fibiger,et al.  On the use of lesions of afferents to localize neurotransmitter receptor sites in the striatum , 1982, Brain Research.

[43]  A. Phillips,et al.  Attenuation by haloperidol of place preference conditioning using food reinforcement , 2004, Psychopharmacology.

[44]  Louis Sokoloff,et al.  Activity‐dependent Energy Metabolism in Rat Posterior Pituitary Primarily Reflects Sodium Pump Activity , 1980, Journal of neurochemistry.

[45]  Larry Stein,et al.  Reinforcement delay of one second severely impairs acquisition of brain self-stimulation , 1985, Brain Research.

[46]  T. Robbins Relationship between reward-enhancing and stereotypical effects of psychomotor stimulant drugs , 1976, Nature.

[47]  N. Ladurelle,et al.  Stimulation of D1 and D2 dopamine receptors produces additive anorectic effects , 1991, Fundamental & clinical pharmacology.

[48]  L. Kerkérian,et al.  Presynaptic dopaminergic control of high affinity glutamate uptake in the striatum , 1983, Neuroscience Letters.

[49]  Theodore W. Berger,et al.  Interactions between dopamine and amino acid-induced excitation and inhibition in the striatum , 1986, Brain Research.

[50]  E. Cherubini,et al.  An inward calcium current underlying regenerative calcium potentials in rat striatal neurons in vitro enhanced by BAY K 8644 , 1987, Neuroscience.

[51]  D. Greenberg,et al.  Striatal calcium channel antagonist receptors in huntington's disease and parkinson's disease , 1988, Annals of neurology.

[52]  M. Ariano Comparison of dopamine binding sites in the rat superior cervical ganglion and caudate nucleus , 1987, Brain Research.

[53]  A. Zharikova,et al.  Role of presynaptic dopamine receptors in regulation of the glutamatergic neurotransmission in rat neostriatum , 1984, Neuroscience.

[54]  P. Greengard,et al.  DARPP-32, a dopamine-regulated phosphoprotein. , 1986, Progress in brain research.

[55]  A. Scheibel,et al.  Biological substrates of schizophrenia , 1986, Acta neurologica Scandinavica.

[56]  J. Lehmann,et al.  The striatal cholinergic interneuron: Synaptic target of dopaminergic terminals? , 1983, Neuroscience.

[57]  J. Joyce,et al.  Striatal topography of D-2 receptors correlates with indexes of cholinergic neuron localization , 1985, Neuroscience Letters.

[58]  Motohiro Kato,et al.  Alterations in local cerebral glucose utilization during electrical stimulation of the striatum and globus pallidus in rats , 1988, Brain Research.

[59]  J. Stellar,et al.  The Neurobiology of Motivation and Reward , 1985 .

[60]  Samuel Thayer,et al.  The effects of excitatory amino acids on intracellular calcium in single mouse striatal neurons in vitro , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[61]  J. Scheel-Krüger,et al.  Dopamine-GABA interactions: evidence that GABA transmits, modulates and mediates dopaminergic functions in the basal ganglia and the limbic system. , 1986, Acta neurologica Scandinavica. Supplementum.

[62]  G E Alexander,et al.  The contribution of basal ganglia to limb control. , 1986, Progress in brain research.

[63]  J. Brown,et al.  The electrophysiology of dopamine (D2) receptors: A study of the actions of dopamine on corticostriatal transmission , 1983, Neuroscience.

[64]  U. Ungerstedt,et al.  Supersensitivity to apomorphine following destruction of the ascending dopamine neurons: quantification using the rotational model. , 1977, European journal of pharmacology.

[65]  J. Eccles Calcium in long-term potentiation as a model for memory , 1983, Neuroscience.

[66]  R. Beninger The role of dopamine in locomotor activity and learning , 1983, Brain Research Reviews.

[67]  R. Beninger,et al.  Receptor subtype-specific dopaminergic agents and conditioned behavior , 1989, Neuroscience & Biobehavioral Reviews.

[68]  G. Mogenson,et al.  Electrophysiological study of the effects of D1 and D2 dopamine antagonists on the interaction of converging inputs from the sensory-motor cortex and substantia nigra neurons in the rat , 1986, Neuroscience.

[69]  J. H. Carlson,et al.  Stimulation of both D1 and D2 dopamine receptors appears necessary for full expression of postsynaptic effects of dopamine agonists: a neurophysiological study , 1987, Brain Research.

[70]  Richard S. Sutton,et al.  Neuronlike adaptive elements that can solve difficult learning control problems , 1983, IEEE Transactions on Systems, Man, and Cybernetics.

[71]  M. Chesselet,et al.  Presynaptic regulation of neurotransmitter release in the brain: Facts and hypothesis , 1984, Neuroscience.

[72]  R. C. Collins,et al.  Effects of dopaminergic stimulation on functional brain metabolism in rats with unilateral substantia nigra lesions , 1983, Brain Research.

[73]  C. Naranjo,et al.  Nifedipine delays the acquisition of tolerance to ethanol. , 1987, European journal of pharmacology.

[74]  Stephen J. Smith,et al.  NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones , 1986, Nature.

[75]  P. Teitelbaum,et al.  The morphogenesis of stereotyped behavior induced by the dopamine receptor agonist apomorphine in the laboratory rat , 1985, Neuroscience.

[76]  G. Robertson,et al.  Synergistic effects of D1 and D2 dopamine agonists on turning behaviour in rats , 1986, Brain Research.

[77]  P. Herrling,et al.  Iontophoretically applied dopamine depolarizes and hyperpolarizes the membrane of cat caudate neurons , 1980, Brain Research.

[78]  Bernard Widrow,et al.  Punish/Reward: Learning with a Critic in Adaptive Threshold Systems , 1973, IEEE Trans. Syst. Man Cybern..

[79]  P. Stanzione,et al.  Excitatory amino acids in synaptic excitation of rat striatal neurones in vitro. , 1988, The Journal of physiology.

[80]  P. Greengard,et al.  Chapter 13 DARPP-32, a dopamine-regulated phosphoprotein , 1986 .

[81]  A. Gerall,et al.  Acquisition and extinction of an instrumental response as a function of delay of intracranial stimulation reward and amount of training , 1970 .

[82]  C. Goetz,et al.  The effect of antimuscarinic agents on haloperidol induced behavioral hypersensitivity. , 1986, European journal of pharmacology.

[83]  K. Starke,et al.  Are presynaptic dopamine autoreceptors and postsynaptic dopamine receptors in the rabbit caudate nucleus pharmacologically different? , 1982, Neuroscience.

[84]  T. Ott,et al.  Modulation by dopaminergic and serotonergic systems of cholinergic interneurons in nucleus accumbens and striatum. , 1985, Polish journal of pharmacology and pharmacy.

[85]  T. F. Freund,et al.  Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines , 1984, Neuroscience.

[86]  C. Fahlke,et al.  Biochemical and behavioral evidence for an interaction between ethanol and calcium channel antagonists , 2005, Journal of Neural Transmission.

[87]  R. Wise,et al.  Relative effectiveness of pimozide, haloperidol and trifluoperazine on self-stimulation rate-intensity functions , 1985, Pharmacology Biochemistry and Behavior.

[88]  C. Y. Yim,et al.  Excitatory input from sensory motor cortex to neostriatum and its modification by conditioning stimulation of the substantia nigra , 1984, Brain Research.

[89]  D. Triggle,et al.  Kainic acid lesions decrease striatal dopamine receptors and 1,4-dihydropyridine sites , 1988, Neuroscience Letters.

[90]  A. Phillips,et al.  The role of dopamine in intracranial self-stimulation of the ventral tegmental area , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[91]  G. Graveland,et al.  A Golgi study of the human neostriatum: Neurons and afferent fibers , 1985, The Journal of comparative neurology.

[92]  Wolfram Schultz,et al.  Depletion of dopamine in the striatum as an experimental model of parkinsonism: direct effects and adaptive mechanisms , 1982, Progress in Neurobiology.

[93]  S. Dolin,et al.  Increased dihydropyridine-sensitive calcium channels in rat brain may underlie ethanol physical dependence , 1987, Neuropharmacology.

[94]  J. Larsen,et al.  The influence of fatigue on health‐related quality of life in patients with Parkinson's disease , 2003, Acta neurologica Scandinavica.

[95]  P. Herrling Pharmacology of the corticocaudate excitatory postsynaptic potential in the cat: Evidence for its mediation by quisqualateor kainate-receptors , 1985, Neuroscience.

[96]  H. T. Chang,et al.  Origins of postsynaptic potentials evoked in identified rat neostriatal neurons by stimulation in substantia nigra , 2004, Experimental Brain Research.

[97]  R. Wise,et al.  The role of reward pathways in the development of drug dependence. , 1987, Pharmacology & therapeutics.

[98]  C. Tanaka,et al.  D2‐dopamine receptor‐mediated inhibition of intracellular Ca2+ mobilization and release of acetylcholine from guinea‐pig neostriatal slices , 1987, British Journal of Pharmacology.

[99]  S. Nakajima,et al.  Reduction of the rewarding effect of brain stimulation by a blockade of dopamine D1 receptor with SCH 23390 , 1986, Pharmacology Biochemistry and Behavior.

[100]  J. Kornhuber,et al.  Presynaptic dopaminergic modulation of cortical input to the striatum. , 1986, Life sciences.

[101]  G. F. Rowlands,et al.  Activation of dopamine receptors inhibits calcium-dependent glutamate release from cortico--striatal terminals in vitro. , 1980, European journal of pharmacology.

[102]  G. Levi,et al.  Dopamine decreases cell excitability in rat striatal neurons by pre- and postsynaptic mechanisms , 1985, Brain Research.

[103]  M. Le Moal,et al.  Interaction between Endogenous Opioids and Dopamine within the Nucleus Accumbens a , 1992, Annals of the New York Academy of Sciences.

[104]  S. Kurumiya,et al.  Dopamine D1 receptors in the nucleus accumbens: involvement in the reinforcing effect of tegmental stimulation , 1988, Brain Research.

[105]  M. Palmer,et al.  Effects of dopamine on spontaneous and evoked activity of caudate neurons , 1983, Neuropharmacology.

[106]  I. Hanbauer,et al.  Evidence for a Selective Localization of Voltage‐Sensitive Ca2+ Channels in Nerve Cell Bodies of Corpus Striatum , 1986, Journal of neurochemistry.

[107]  M. Moloney Excitatory Amino Acids. , 2010 .

[108]  R. Beninger,et al.  Receptor subtype-specific dopaminergic agents and unconditioned behavior. , 1991, Polish journal of pharmacology and pharmacy.

[109]  E. Hilgard,et al.  Conditioning and Learning , 1940 .

[110]  G. Di Chiara,et al.  Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[111]  J D Connor,et al.  Caudate nucleus neurones: correlation of the effects of substantia nigra stimulation with iontophoretic dopamine , 1970, The Journal of physiology.

[112]  W. Klemm,et al.  Dopaminergic mediation of reward: Evidence gained using a natural reinforcer in a behavioral contrast paradigm , 1981, Neuroscience Letters.

[113]  T. Craig,et al.  Neuroleptics, extrapyramidal symptoms, and serum-calcium levels. , 1984, Comprehensive psychiatry.

[114]  P R Mitchell,et al.  Modulation of striatal [3H]-glutamic acid release by dopaminergic drugs. , 1980, Life sciences.

[115]  P. Somogyi,et al.  Monosynaptic cortical input and local axon collaterals of identified striatonigral neurons. A light and electron microscopic study using the golgi‐peroxidase transport‐degeneration procedure , 1981, The Journal of comparative neurology.

[116]  P. Groves A theory of the functional organization of the neostriatum and the neostriatal control of voluntary movement , 1983, Brain Research Reviews.

[117]  S. Janković,et al.  The effects of excitatory amino acids on isolated gut segments of the rat. , 1999, Pharmacological research.

[118]  M. Reivich,et al.  THE [14C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1 , 1977, Journal of neurochemistry.

[119]  C. Gallistel,et al.  Affinity for the dopamine D2 receptor predicts neuroleptic potency in blocking the reinforcing effect of MFB stimulation , 1983, Pharmacology Biochemistry and Behavior.