Modulation of Long-Term Depression by Dopamine in the Mesolimbic System

Long-lasting adaptations in the mesolimbic dopamine (DA) system in response to drugs of abuse likely mediate many of the behavioral changes that underlie addiction. Recent work suggests that long-term changes in synaptic strength at excitatory synapses in the two major components of this system, the nucleus accumbens (NAc) and ventral tegmental area, may be particularly important for the development of drug-induced sensitization, a process that may contribute to addiction, as well as for normal response-reinforcement learning. Using whole-cell patch-clamp recording techniques fromin vitro slice preparations, we have examined the existence and basic mechanisms of long-term depression (LTD) at excitatory synapses on both GABAergic medium spiny neurons in the NAc and dopaminergic neurons in the midbrain. We find that both sets of synapses express LTD but that their basic triggering mechanisms differ. Furthermore, DA blocks the induction of LTD in the midbrain via activation of D2-like receptors but has minimal effects on LTD in the NAc. The existence of LTD in mesolimbic structures and its modulation by DA represent mechanisms that may contribute to the modifications of neural circuitry that mediate reward-related learning as well as the development of addiction.

[1]  Sun-spots and Terrestrial Magnetism , 1878, Nature.

[2]  T. Sejnowski,et al.  Storing covariance with nonlinearly interacting neurons , 1977, Journal of mathematical biology.

[3]  Douglas L. Jones,et al.  From motivation to action: Functional interface between the limbic system and the motor system , 1980, Progress in Neurobiology.

[4]  T. Robinson,et al.  Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis , 1986, Brain Research Reviews.

[5]  S. Heinemann,et al.  Ca2+ permeability of KA-AMPA--gated glutamate receptor channels depends on subunit composition , 1991, Science.

[6]  P. Kalivas,et al.  Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity , 1991, Brain Research Reviews.

[7]  R. North,et al.  Two types of neurone in the rat ventral tegmental area and their synaptic inputs. , 1992, The Journal of physiology.

[8]  P. Calabresi,et al.  Long-term synaptic depression in the striatum: physiological and pharmacological characterization , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  K. Berridge,et al.  The neural basis of drug craving: An incentive-sensitization theory of addiction , 1993, Brain Research Reviews.

[10]  J. Luebke,et al.  Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus , 1993, Neuron.

[11]  F. H. Lopes da Silva,et al.  Synaptic Plasticity in an In Vitro Slice Preparation of the Rat Nucleus Accumbens , 1993, The European journal of neuroscience.

[12]  R. Nicoll,et al.  NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms , 1993, Trends in Neurosciences.

[13]  R. Malenka,et al.  Simultaneous LTP of non-NMDA- and LTD of NMDA-receptor-mediated responses in the nucleus accumbens , 1994, Nature.

[14]  R. Tsien,et al.  Roles of N-type and Q-type Ca2+ channels in supporting hippocampal synaptic transmission. , 1994, Science.

[15]  B. Bean,et al.  Voltage-dependent calcium channels in rat midbrain dopamine neurons: modulation by dopamine and GABAB receptors. , 1995, Journal of neurophysiology.

[16]  J. Bockaert,et al.  Phenylglycine derivatives discriminate between mGluR1- and mGluR5-mediated responses , 1995, Neuropharmacology.

[17]  W. Singer.  Development and plasticity of cortical processing architectures. , 1995, Science.

[18]  C. Shatz,et al.  Synaptic Activity and the Construction of Cortical Circuits , 1996, Science.

[19]  R. Nicoll,et al.  Ca2+ Signaling Requirements for Long-Term Depression in the Hippocampus , 1996, Neuron.

[20]  P. Dayan,et al.  A framework for mesencephalic dopamine systems based on predictive Hebbian learning , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  M. Bear,et al.  Long-term depression in hippocampus. , 1996, Annual review of neuroscience.

[22]  R. Malenka,et al.  Psychostimulants depress excitatory synaptic transmission in the nucleus accumbens via presynaptic D1-like dopamine receptors , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  T. Robbins,et al.  Neurobehavioural mechanisms of reward and motivation , 1996, Current Opinion in Neurobiology.

[24]  Peter Dayan,et al.  A Neural Substrate of Prediction and Reward , 1997, Science.

[25]  S. Smith‐Roe,et al.  Response-reinforcement learning is dependent on N-methyl-D-aspartate receptor activation in the nucleus accumbens core. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Malenka,et al.  Dopamine Depresses Excitatory and Inhibitory Synaptic Transmission by Distinct Mechanisms in the Nucleus Accumbens , 1997, The Journal of Neuroscience.

[27]  G F Koob,et al.  Drug abuse: hedonic homeostatic dysregulation. , 1997, Science.

[28]  R. Nicoll,et al.  Two Distinct Forms of Long-Term Depression Coexist in CA1 Hippocampal Pyramidal Cells , 1997, Neuron.

[29]  R. Dingledine,et al.  Differential Dependence on GluR2 Expression of Three Characteristic Features of AMPA Receptors , 1997, The Journal of Neuroscience.

[30]  G. Aghajanian,et al.  Molecular and cellular basis of addiction. , 1997, Science.

[31]  R. Wise.  Drug-activation of brain reward pathways. , 1998, Drug and alcohol dependence.

[32]  Pankaj Sah,et al.  Calcium-permeable AMPA receptors mediate long-term potentiation in interneurons in the amygdala , 1998, Nature.

[33]  S. R. Nash,et al.  Dopamine receptors: from structure to function. , 1998, Physiological reviews.

[34]  M. West,et al.  Tonic inhibition of single nucleus accumbens neurons in the rat: a predominant but not exclusive firing pattern induced by cocaine self-administration sessions , 1998, Neuroscience.

[35]  P. Overton,et al.  Alterations in excitatory amino acid‐mediated regulation of midbrain dopaminergic neurones induced by chronic psychostimulant administration and stress: relevance to behavioural sensitization and drug addiction , 1998, Addiction biology.

[36]  M. Wolf,et al.  The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants , 1998, Progress in Neurobiology.

[37]  P. Kalivas,et al.  Neuroadaptations involved in amphetamine and cocaine addiction. , 1998, Drug and alcohol dependence.

[38]  M. Bear,et al.  Effects of the Metabotropic Glutamate Receptor Antagonist MCPG on Phosphoinositide Turnover and Synaptic Plasticity in Visual Cortex , 1998, The Journal of Neuroscience.

[39]  R. Malenka,et al.  Modulation of synaptic transmission by dopamine and norepinephrine in ventral but not dorsal striatum. , 1998, Journal of neurophysiology.

[40]  R. Malenka,et al.  Properties and Plasticity of Excitatory Synapses on Dopaminergic and GABAergic Cells in the Ventral Tegmental Area , 1999, The Journal of Neuroscience.

[41]  P. Overton,et al.  Long-term potentiation at excitatory amino acid synapses on midbrain dopamine neurons. , 1999, Neuroreport.

[42]  D. Jane,et al.  Pharmacological agents acting at subtypes of metabotropic glutamate receptors , 1999, Neuropharmacology.

[43]  J. Kauer,et al.  Amphetamine Depresses Excitatory Synaptic Transmission via Serotonin Receptors in the Ventral Tegmental Area , 1999, The Journal of Neuroscience.

[44]  R. Dingledine,et al.  Long-term depression in hippocampal interneurons: joint requirement for pre- and postsynaptic events. , 1999, Science.

[45]  T. Robbins,et al.  Dissociation in Effects of Lesions of the Nucleus Accumbens Core and Shell on Appetitive Pavlovian Approach Behavior and the Potentiation of Conditioned Reinforcement and Locomotor Activity byd-Amphetamine , 1999, The Journal of Neuroscience.

[46]  L. Stinus,et al.  d-Amphetamine-induced behavioral sensitization: implication of a glutamatergic medial prefrontal cortex–ventral tegmental area innervation , 1999, Neuroscience.

[47]  M. Bear.  Homosynaptic long-term depression: a mechanism for memory? , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[48]  J. Kauer,et al.  Amphetamine Blocks Long-Term Synaptic Depression in the Ventral Tegmental Area , 2000, The Journal of Neuroscience.

[49]  A. Kelley,et al.  N-methyl-D-aspartate receptor-dependent plasticity within a distributed corticostriatal network mediates appetitive instrumental learning. , 2000, Behavioral neuroscience.

[50]  N-methyl-D-aspartate receptor-dependent plasticity within a distributed corticostriatal network mediates appetitive instrumental learning. , 2000 .