Faculty Opinions recommendation of Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens.

Stearate-modified graphite paste electrodes were implanted chronically into dopamine terminal regions in the nucleus accumbens or caudate nucleus of the rat. Reverse dialysis was used to demonstrate a selective response of these electrodes to dopamine, but not 3,4-dihydroxyphenylacetic acid or ascorbic acid. In a separate behavioural experiment, a significant increase in the chronoamperometric response was observed during presentation of a conditional stimulus predictive of food, and the electrochemical response remained elevated during and following consumption of the meal. Similar trends were observed from electrodes in the caudate nucleus. These data confirm the activation of mesolimbic dopamine neurons by incentive stimuli predictive of food and possibly by consumption of food. Together with other recent data on sex- and thirst-related increases in dopamine levels in the nucleus accumbens, these findings are consistent with a role for the nucleus accumbens as an interface between motivation and activation of the motor system.Key words: dopamine, nucleus accumbens, electrochemistry, feeding, conditional response.

Download Full-text

Functional interaction of dopamine and glutamate in the nucleus accumbens in the regulation of locomotion

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y93-061 ◽

1993 ◽

Vol 71 (5-6) ◽

pp. 407-413 ◽

Cited By ~ 60

Author(s):

Michael Wu ◽

Stefan M. Brudzynski ◽

Gordon J. Mogenson

Keyword(s):

Locomotor Activity ◽

Nucleus Accumbens ◽

Nmda Receptor ◽

Aspartic Acid ◽

Receptor Agonist ◽

Dopamine Neurons ◽

Mesolimbic Dopamine ◽

Axon Terminals ◽

6 Hydroxydopamine ◽

Dose Dependent

The interaction of dopamine and glutamate in the nucleus accumbens in the regulation of locomotion was investigated. Microinjection of N-methyl-D-aspartic acid (NMDA, a glutamatergic NMDA receptor agonist) or α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, a quisqualic receptor agonist which is a glutamatergic non-NMDA receptor agonist) into the nucleus accumbens caused a substantial increase in locomotor activity. This increase in locomotor activity was significantly reduced by prior administration of the dopamine D2 agonist quinpirole, but not the D1 agonist, SKF 38393, into the same brain sites. The reduction in locomotion produced by quinpirole was dose dependent. Eight days after the ventral tegmental area was lesioned with 6-hydroxydopamine to destroy the dopamine projection and the axon terminals of the mesolimbic dopamine neurons in nucleus accumbens, the hyperkinetic effects produced by injections of NMDA and AMPA into the nucleus accumbens were substantially reduced. These results suggested that the glutamate agonist induced locomotion is mediated by dopamine. Thus, it appears that NMDA- or AMPA-induced locomotion is due to the activation of glutamate receptors on the mesolimbic dopamine terminals in the nucleus accumbens which release dopamine and subsequently increase locomotion.Key words: nucleus accumbens, dopamine, glutamate, quinpirole, locomotion, N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid.

Download Full-text

Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts

Nature Communications ◽

10.1038/s41467-020-17543-4 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Milan D. Valyear ◽

Iulia Glovaci ◽

Audrey Zaari ◽

Soraya Lahlou ◽

Ivan Trujillo-Pisanty ◽

...

Keyword(s):

Animal Model ◽

Substance Use ◽

Nucleus Accumbens ◽

Conditioned Stimulus ◽

Substance Use Disorder ◽

Dopamine Neurons ◽

Environmental Cues ◽

Mesolimbic Dopamine ◽

Dopamine Circuits ◽

Alcohol Seeking

Abstract Context can influence reactions to environmental cues and this elemental process has implications for substance use disorder. Using an animal model, we show that an alcohol-associated context elevates entry into a fluid port triggered by a conditioned stimulus (CS) that predicted alcohol (CS-triggered alcohol-seeking). This effect persists across multiple sessions and, after it diminishes in extinction, the alcohol context retains the capacity to augment reinstatement. Systemically administered eticlopride and chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons reduce CS-triggered alcohol-seeking. Chemogenetically silencing VTA dopamine terminals in the nucleus accumbens (NAc) core reduces CS-triggered alcohol-seeking, irrespective of context, whereas silencing VTA dopamine terminals in the NAc shell selectively reduces the elevation of CS-triggered alcohol-seeking in an alcohol context. This dissociation reveals new roles for divergent mesolimbic dopamine circuits in the control of responding to a discrete cue for alcohol and in the amplification of this behaviour in an alcohol context.

Download Full-text

Divergent mesolimbic dopamine circuits support alcohol-seeking triggered by discrete cues and contexts

10.1101/475343 ◽

2018 ◽

Cited By ~ 3

Author(s):

M.D. Valyear ◽

I. Glovaci ◽

A. Zaari ◽

S. Lahlou ◽

I. Trujillo-Pisanty ◽

...

Keyword(s):

Nucleus Accumbens ◽

Ventral Tegmental Area ◽

Neural Mechanisms ◽

Dopamine Neurons ◽

Environmental Cues ◽

Contextual Cues ◽

Mesolimbic Dopamine ◽

Neutral Context ◽

Dopamine Circuits ◽

Alcohol Seeking

ABSTRACTDiscrete and contextual cues that predict alcohol trigger alcohol-seeking. However, the extent to which context influences alcohol-seeking triggered by discrete cues, and the neural mechanisms underlying these responses, are not well known. We show that, relative to a neutral context, a context associated with alcohol persistently elevated alcohol-seeking triggered by a discrete cue, and supported higher levels of priming-induced reinstatement. Alcohol-seeking triggered by a discrete cue in a neutral context was reduced by designer receptor-mediated inhibition of ventral tegmental area (VTA) dopamine neurons in TH::Cre rats. Inhibiting terminals of VTA dopamine neurons in the nucleus accumbens (NAc) core reduced alcohol-seeking triggered by a discrete cue, irrespective of context, whereas inhibiting VTA dopamine terminals in the NAc shell selectively reduced the elevation of alcohol-seeking triggered by a discrete cue in an alcohol context. This dissociation highlights unique roles for divergent mesolimbic dopamine circuits in alcohol-seeking driven by discrete and contextual environmental cues.

Download Full-text

Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction in mice

Nature Communications ◽

10.1038/s41467-021-23040-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Andrew J. Kesner ◽

Rick Shin ◽

Coleman B. Calva ◽

Reuben F. Don ◽

Sue Junn ◽

...

Keyword(s):

Ventral Tegmental Area ◽

Dopamine Neurons ◽

Theta Oscillations ◽

Mesolimbic Dopamine ◽

Sucrose Consumption ◽

Behavioral Interaction ◽

Hypothalamic Structure ◽

Hippocampal Theta ◽

Substances Of Abuse ◽

Stimulation Of

AbstractThe supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.

Download Full-text

Amphetamine Activation of Hippocampal Drive of Mesolimbic Dopamine Neurons: A Mechanism of Behavioral Sensitization

Journal of Neuroscience ◽

10.1523/jneurosci.1582-08.2008 ◽

2008 ◽

Vol 28 (31) ◽

pp. 7876-7882 ◽

Cited By ~ 85

Author(s):

D. J. Lodge ◽

A. A. Grace

Keyword(s):

Behavioral Sensitization ◽

Dopamine Neurons ◽

Mesolimbic Dopamine

Download Full-text

Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement

10.1101/385039 ◽

2018 ◽

Author(s):

Julie Corre ◽

Ruud van Zessen ◽

Michaël Loureiro ◽

Tommaso Patriarchi ◽

Lin Tian ◽

...

Keyword(s):

Nucleus Accumbens ◽

Causal Link ◽

The Self ◽

Dopamine Neurons ◽

Self Administration ◽

Gaba Neurons ◽

Calcium Indicators ◽

Compulsive Consumption ◽

Self Stimulation ◽

Stimulation Of

AbstractThe dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we use genetically encoded DA and calcium indicators as well as cFos to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement.

Download Full-text

Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens

Brain Structure and Function ◽

10.1007/s00429-021-02449-8 ◽

2022 ◽

Author(s):

Imre Kalló ◽

Azar Omrani ◽

Frank J. Meye ◽

Han de Jong ◽

Zsolt Liposits ◽

...

Keyword(s):

Prefrontal Cortex ◽

Nucleus Accumbens ◽

Ventral Tegmental Area ◽

Medial Prefrontal Cortex ◽

Fluorescent Protein ◽

Yellow Fluorescent Protein ◽

Dopamine Neurons ◽

Regulatory Processes ◽

Ventral Tegmental ◽

Shell Part

AbstractOrexin neurons are involved in homeostatic regulatory processes, including arousal and feeding, and provide a major input from the hypothalamus to the ventral tegmental area (VTA) of the midbrain. VTA neurons are a central hub processing reward and motivation and target the medial prefrontal cortex (mPFC) and the shell part of nucleus accumbens (NAcs). We investigated whether subpopulations of dopamine (DA) neurons in the VTA projecting either to the mPFC or the medial division of shell part of nucleus accumbens (mNAcs) receive differential input from orexin neurons and whether orexin exerts differential electrophysiological effects upon these cells. VTA neurons projecting to the mPFC or the mNAcs were traced retrogradely by Cav2-Cre virus and identified by expression of yellow fluorescent protein (YFP). Immunocytochemical analysis showed that a higher proportion of all orexin-innervated DA neurons projected to the mNAcs (34.5%) than to the mPFC (5.2%). Of all sampled VTA neurons projecting either to the mPFC or mNAcs, the dopaminergic (68.3 vs. 79.6%) and orexin-innervated DA neurons (68.9 vs. 64.4%) represented the major phenotype. Whole-cell current clamp recordings were obtained from fluorescently labeled neurons in slices during baseline periods and bath application of orexin A. Orexin similarly increased the firing rate of VTA dopamine neurons projecting to mNAcs (1.99 ± 0.61 Hz to 2.53 ± 0.72 Hz) and mPFC (0.40 ± 0.22 Hz to 1.45 ± 0.56 Hz). Thus, the hypothalamic orexin system targets mNAcs and to a lesser extent mPFC-projecting dopaminergic neurons of the VTA and exerts facilitatory effects on both clusters of dopamine neurons.

Download Full-text