TY - JOUR
T1 - Divergent activation of ventromedial and ventrolateral dopamine systems in animal models of amphetamine sensitization and schizophrenia
AU - Lodge, Daniel J.
AU - Grace, Anthony A.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/2
Y1 - 2012/2
N2 - Aberrant dopamine-mediated behaviours are a hallmark of a number of psychiatric disorders, including substance use disorders and schizophrenia. It has been demonstrated recently that rodent models of these diseases display enhanced dopamine neuron activity throughout the ventral tegmental area (VTA). It is known, however, that the VTA is not a homogeneous structure, and that the dopamine neuron population provides discrete, topographical innervation of nucleus accumbens subregions. In addition, these ventromedial and ventrolateral dopamine systems are known to subserve complementary but distinct aspects of goal-directed behaviour. Using in-vivo extracellular recordings of identified dopamine neurons in chloral hydrate-anaesthetized rats, we examined the level of dopamine neuron population activity across the mediolateral extent of the VTA following amphetamine sensitization or gestational methylazoxymethanol acetate (MAM) treatment, a verified rodent model of schizophrenia. Here we demonstrate that both models display an augmented medial VTA-ventromedial striatal dopamine system function that correlates with the augmented locomotor response to amphetamine observed in both models. In contrast, only MAM-treated rats exhibit an increase in VTA-ventrolateral striatal dopamine system function. This latter finding is consistent with human imaging studies in schizophrenia patients. In summary, we demonstrate that, although a number of disorders involving a hyperdopaminergic state demonstrate an increase in dopamine neuron population activity, there is divergence in the exact populations of neurons affected. This distinction probably underlies the observed differences in disease symptomatology.
AB - Aberrant dopamine-mediated behaviours are a hallmark of a number of psychiatric disorders, including substance use disorders and schizophrenia. It has been demonstrated recently that rodent models of these diseases display enhanced dopamine neuron activity throughout the ventral tegmental area (VTA). It is known, however, that the VTA is not a homogeneous structure, and that the dopamine neuron population provides discrete, topographical innervation of nucleus accumbens subregions. In addition, these ventromedial and ventrolateral dopamine systems are known to subserve complementary but distinct aspects of goal-directed behaviour. Using in-vivo extracellular recordings of identified dopamine neurons in chloral hydrate-anaesthetized rats, we examined the level of dopamine neuron population activity across the mediolateral extent of the VTA following amphetamine sensitization or gestational methylazoxymethanol acetate (MAM) treatment, a verified rodent model of schizophrenia. Here we demonstrate that both models display an augmented medial VTA-ventromedial striatal dopamine system function that correlates with the augmented locomotor response to amphetamine observed in both models. In contrast, only MAM-treated rats exhibit an increase in VTA-ventrolateral striatal dopamine system function. This latter finding is consistent with human imaging studies in schizophrenia patients. In summary, we demonstrate that, although a number of disorders involving a hyperdopaminergic state demonstrate an increase in dopamine neuron population activity, there is divergence in the exact populations of neurons affected. This distinction probably underlies the observed differences in disease symptomatology.
KW - Amphetamine sensitization
KW - associative striatum
KW - dopamine
KW - nucleus accumbens
KW - schizophrenia
KW - stress
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U2 - 10.1017/S1461145711000113
DO - 10.1017/S1461145711000113
M3 - Article
C2 - 21329556
AN - SCOPUS:84856484885
VL - 15
SP - 69
EP - 76
JO - The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
JF - The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
SN - 1461-1457
IS - 1
ER -