Optical suppression of drug-evoked phasic dopamine release

Brief fluctuations in dopamine concentration (dopamine transients) play a key role in behavior towards rewards, including drugs of abuse. Drug-evoked dopamine transients may result from actions at both dopamine cell bodies and dopamine terminals. Inhibitory opsins can be targeted to dopamine neurons permitting their firing activity to be suppressed. However, as dopamine transients can become uncoupled from firing, it is unknown whether optogenetic hyperpolarization at the level of the soma is able to suppress dopamine transients. Here, we used in vivo fast-scan cyclic voltammetry to record transients evoked by cocaine and raclopride in nucleus accumbens (NAc) of urethane-anesthetized rats. We targeted halorhodopsin (NpHR) specifically to dopamine cells by injecting Cre-inducible virus into ventral tegmental area (VTA) of transgenic rats that expressed Cre recombinase under control of the tyrosine hydroxylase promoter (TH-Cre+ rats). Consistent with previous work, co-administration of cocaine and raclopride led to the generation of dopamine transients in NAc shell. Illumination of VTA with laser strongly suppressed the frequency of transients in NpHR-expressing rats, but not in control rats. Laser did not have any effect on amplitude of transients. Thus, optogenetics can effectively reduce the occurrence of drug-evoked transients and is therefore a suitable approach for studying the functional role of such transients in drug-associated behavior.

[1]  K. Gysling,et al.  Morphine-induced activation of A10 dopamine neurons in the rat , 1983, Brain Research.

[2]  G. Gessa,et al.  Preferential stimulation of ventral tegmental area dopaminergic neurons by nicotine. , 1987, European journal of pharmacology.

[3]  G. Gessa,et al.  Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors. , 1998, European journal of pharmacology.

[4]  M. Brodie,et al.  Ethanol directly excites dopaminergic ventral tegmental area reward neurons. , 1999, Alcoholism, clinical and experimental research.

[5]  R. Wightman,et al.  Subsecond dopamine release promotes cocaine seeking , 2003, Nature.

[6]  R. Wightman,et al.  Cannabinoids Enhance Subsecond Dopamine Release in the Nucleus Accumbens of Awake Rats , 2004, The Journal of Neuroscience.

[7]  R. Wightman,et al.  Resolving neurotransmitters detected by fast-scan cyclic voltammetry. , 2004, Analytical chemistry.

[8]  W. Shi,et al.  Psychostimulants Induce Low-Frequency Oscillations in the Firing Activity of Dopamine Neurons , 2004, Neuropsychopharmacology.

[9]  C. Lüscher,et al.  The Mechanistic Classification of Addictive Drugs , 2006, PLoS medicine.

[10]  S. Ikemoto.  Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex , 2007, Brain Research Reviews.

[11]  R. Wightman,et al.  Phasic Dopamine Release Evoked by Abused Substances Requires Cannabinoid Receptor Activation , 2007, The Journal of Neuroscience.

[12]  R. Wightman,et al.  Associative learning mediates dynamic shifts in dopamine signaling in the nucleus accumbens , 2007, Nature Neuroscience.

[13]  R. Wightman,et al.  Pharmacologically induced, subsecond dopamine transients in the caudate–putamen of the anesthetized rat , 2007, Synapse.

[14]  R. Wightman,et al.  Preferential Enhancement of Dopamine Transmission within the Nucleus Accumbens Shell by Cocaine Is Attributable to a Direct Increase in Phasic Dopamine Release Events , 2008, The Journal of Neuroscience.

[15]  R. Wightman,et al.  Real-time chemical responses in the nucleus accumbens differentiate rewarding and aversive stimuli , 2008, Nature Neuroscience.

[16]  S. Cragg,et al.  Presynaptic nicotinic receptors: a dynamic and diverse cholinergic filter of striatal dopamine neurotransmission , 2008, British journal of pharmacology.

[17]  R. Wightman,et al.  Disparity between tonic and phasic ethanol-induced dopamine increases in the nucleus accumbens of rats. , 2009, Alcoholism, clinical and experimental research.

[18]  M. Ungless,et al.  Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli , 2009, Proceedings of the National Academy of Sciences.

[19]  K. Deisseroth,et al.  Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning , 2009, Science.

[20]  R. Wightman,et al.  Synaptic Overflow of Dopamine in the Nucleus Accumbens Arises from Neuronal Activity in the Ventral Tegmental Area , 2009, The Journal of Neuroscience.

[21]  Ilana B. Witten,et al.  Cholinergic Interneurons Control Local Circuit Activity and Cocaine Conditioning , 2010, Science.

[22]  R. Wightman,et al.  Rank estimation and the multivariate analysis of in vivo fast-scan cyclic voltammetric data. , 2010, Analytical chemistry.

[23]  R. Wightman,et al.  In vivo voltammetric monitoring of catecholamine release in subterritories of the nucleus accumbens shell , 2010, Neuroscience.

[24]  J. Tsien,et al.  Convergent Processing of Both Positive and Negative Motivational Signals by the VTA Dopamine Neuronal Populations , 2011, PloS one.

[25]  Ilana B. Witten,et al.  Recombinase-Driver Rat Lines: Tools, Techniques, and Optogenetic Application to Dopamine-Mediated Reinforcement , 2011, Neuron.

[26]  Joshua L. Jones,et al.  Cocaine Cues Drive Opposing Context-Dependent Shifts in Reward Processing and Emotional State , 2011, Biological Psychiatry.

[27]  Ilana B. Witten,et al.  Witten Conditioning Cholinergic Interneurons Control Local Circuit Activity and Cocaine , 2011 .

[28]  M. Marinelli,et al.  Dopamine neurons in the ventral tegmental area fire faster in adolescent rats than in adults. , 2012, Journal of neurophysiology.

[29]  C. Charlier,et al.  Differential Effects of Cocaine on Dopamine Neuron Firing in Awake and Anesthetized Rats , 2012, Neuropsychopharmacology.

[30]  J. McCutcheon,et al.  Encoding of Aversion by Dopamine and the Nucleus Accumbens , 2012, Front. Neurosci..

[31]  C. Akerman,et al.  Optogenetic silencing strategies differ in their effects on inhibitory synaptic transmission , 2012, Nature Neuroscience.

[32]  K. Deisseroth,et al.  Striatal Dopamine Release Is Triggered by Synchronized Activity in Cholinergic Interneurons , 2012, Neuron.

[33]  J. McCutcheon,et al.  Electrode calibration with a microfluidic flow cell for fast-scan cyclic voltammetry. , 2012, Lab on a chip.

[34]  R. Wightman,et al.  Sources contributing to the average extracellular concentration of dopamine in the nucleus accumbens , 2012, Journal of neurochemistry.

[35]  B. Everitt,et al.  Hierarchical recruitment of phasic dopamine signaling in the striatum during the progression of cocaine use , 2012, Proceedings of the National Academy of Sciences.

[36]  G. Stuber,et al.  Activation of VTA GABA Neurons Disrupts Reward Consumption , 2012, Neuron.

[37]  M. Marinelli,et al.  faster in adolescent rats than in adults Dopamine neurons in the ventral tegmental area fire , 2012 .

[38]  Garret D Stuber,et al.  Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits , 2011, Nature Protocols.

[39]  Kelly R. Tan,et al.  GABA Neurons of the VTA Drive Conditioned Place Aversion , 2012, Neuron.

[40]  D. Lovinger,et al.  Selective activation of cholinergic interneurons enhances accumbal phasic dopamine release: setting the tone for reward processing. , 2012, Cell reports.

[41]  Alice M Stamatakis,et al.  Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance , 2012, Nature Neuroscience.

[42]  J. J. Cone,et al.  Prolonged High Fat Diet Reduces Dopamine Reuptake without Altering DAT Gene Expression , 2013, PloS one.

[43]  Aaron S. Andalman,et al.  Dopamine neurons modulate neural encoding and expression of depression-related behaviour , 2012, Nature.

[44]  K. Deisseroth,et al.  Rapid regulation of depression-related behaviors by control of midbrain dopamine neurons , 2012, Nature.

[45]  Tim C. Lei,et al.  Light Scattering Properties Vary across Different Regions of the Adult Mouse Brain , 2013, PloS one.

[46]  Alice M Stamatakis,et al.  Distinct extended amygdala circuits for divergent motivational states , 2013, Nature.

[47]  Josiah R. Boivin,et al.  A Causal Link Between Prediction Errors, Dopamine Neurons and Learning , 2013, Nature Neuroscience.

[48]  David P. Daberkow,et al.  Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals , 2013, The Journal of Neuroscience.

[49]  S. Ikemoto,et al.  Similar Roles of Substantia Nigra and Ventral Tegmental Dopamine Neurons in Reward and Aversion , 2014, The Journal of Neuroscience.

[50]  Steven P. Wilson,et al.  Designer Receptors Show Role for Ventral Pallidum Input to Ventral Tegmental Area in Cocaine Seeking , 2014, Nature Neuroscience.

[51]  S. Nakanishi,et al.  Aversive behavior induced by optogenetic inactivation of ventral tegmental area dopamine neurons is mediated by dopamine D2 receptors in the nucleus accumbens , 2014, Proceedings of the National Academy of Sciences.

[52]  Josiah R. Boivin,et al.  Positive Reinforcement Mediated by Midbrain Dopamine Neurons Requires D1 and D2 Receptor Activation in the Nucleus Accumbens , 2014, PloS one.

[53]  P. Garris,et al.  Illicit dopamine transients: Reconciling actions of abused drugs , 2014, Trends in Neurosciences.