Abstract
Evidence suggests that both genetic and environmental factors contribute to the development of schizophrenia. Rodent models of the disorder have been developed that model either genetic or environment factors to recapitulate various aspects of the disease; however, the examination of gene by environment interactions requires a model of susceptibility. We have previously demonstrated that a proportion of the F2 generation of MAM-treated rats display a schizophrenia-like phenotype, defined as an increase in ventral tegmental area (VTA) dopamine neuron population activity. Here we use this model to examine the consequence of adolescent stress (AS), a known risk factor for psychiatric disease, on dopamine neuron activity in the VTA. Specifically, F2 MAM rats were exposed to predator odor, a stressor of high ethological relevance, intermittently over 10 days throughout the adolescent period and VTA dopamine neuron activity was evaluated in adulthood. Both saline and MAM F2 rats exposed to AS displayed significant increases in population activity; however, the proportion of F2 MAM rats exhibiting this increase was significantly greater (approximately 70%) compared to their respective controls. Given that we have previously demonstrated that the augmented dopamine neuron activity in rodent models of psychosis is directly attributable to aberrant activity in the ventral hippocampus (vHipp), we examined whether AS altered activity within the vHipp. Indeed, there was a positive correlation between dopamine neuron activity and hippocampal firing rates, such that those rats that displayed increases in population activity also had increases in the firing rates of vHipp putative pyramidal neurons. Taken together, these data further demonstrate a role for AS as a risk factor for psychosis, particularly in those with a heritable predisposition.
| Original language | English (US) |
|---|---|
| Article number | 109701 |
| Journal | Progress in Neuro-Psychopharmacology and Biological Psychiatry |
| Volume | 95 |
| DOIs | |
| State | Published - Dec 20 2019 |
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Keywords
- Adolescent stress
- F2 generation
- Hippocampus
- MAM
- Schizophrenia
ASJC Scopus subject areas
- Pharmacology
- Biological Psychiatry
Cite this
Adolescent stress contributes to aberrant dopamine signaling in a heritable rodent model of susceptibility. / Perez, Stephanie M.; Lodge, Daniel J.
In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 95, 109701, 20.12.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Adolescent stress contributes to aberrant dopamine signaling in a heritable rodent model of susceptibility
AU - Perez, Stephanie M.
AU - Lodge, Daniel J
PY - 2019/12/20
Y1 - 2019/12/20
N2 - Evidence suggests that both genetic and environmental factors contribute to the development of schizophrenia. Rodent models of the disorder have been developed that model either genetic or environment factors to recapitulate various aspects of the disease; however, the examination of gene by environment interactions requires a model of susceptibility. We have previously demonstrated that a proportion of the F2 generation of MAM-treated rats display a schizophrenia-like phenotype, defined as an increase in ventral tegmental area (VTA) dopamine neuron population activity. Here we use this model to examine the consequence of adolescent stress (AS), a known risk factor for psychiatric disease, on dopamine neuron activity in the VTA. Specifically, F2 MAM rats were exposed to predator odor, a stressor of high ethological relevance, intermittently over 10 days throughout the adolescent period and VTA dopamine neuron activity was evaluated in adulthood. Both saline and MAM F2 rats exposed to AS displayed significant increases in population activity; however, the proportion of F2 MAM rats exhibiting this increase was significantly greater (approximately 70%) compared to their respective controls. Given that we have previously demonstrated that the augmented dopamine neuron activity in rodent models of psychosis is directly attributable to aberrant activity in the ventral hippocampus (vHipp), we examined whether AS altered activity within the vHipp. Indeed, there was a positive correlation between dopamine neuron activity and hippocampal firing rates, such that those rats that displayed increases in population activity also had increases in the firing rates of vHipp putative pyramidal neurons. Taken together, these data further demonstrate a role for AS as a risk factor for psychosis, particularly in those with a heritable predisposition.
AB - Evidence suggests that both genetic and environmental factors contribute to the development of schizophrenia. Rodent models of the disorder have been developed that model either genetic or environment factors to recapitulate various aspects of the disease; however, the examination of gene by environment interactions requires a model of susceptibility. We have previously demonstrated that a proportion of the F2 generation of MAM-treated rats display a schizophrenia-like phenotype, defined as an increase in ventral tegmental area (VTA) dopamine neuron population activity. Here we use this model to examine the consequence of adolescent stress (AS), a known risk factor for psychiatric disease, on dopamine neuron activity in the VTA. Specifically, F2 MAM rats were exposed to predator odor, a stressor of high ethological relevance, intermittently over 10 days throughout the adolescent period and VTA dopamine neuron activity was evaluated in adulthood. Both saline and MAM F2 rats exposed to AS displayed significant increases in population activity; however, the proportion of F2 MAM rats exhibiting this increase was significantly greater (approximately 70%) compared to their respective controls. Given that we have previously demonstrated that the augmented dopamine neuron activity in rodent models of psychosis is directly attributable to aberrant activity in the ventral hippocampus (vHipp), we examined whether AS altered activity within the vHipp. Indeed, there was a positive correlation between dopamine neuron activity and hippocampal firing rates, such that those rats that displayed increases in population activity also had increases in the firing rates of vHipp putative pyramidal neurons. Taken together, these data further demonstrate a role for AS as a risk factor for psychosis, particularly in those with a heritable predisposition.
KW - Adolescent stress
KW - F2 generation
KW - Hippocampus
KW - MAM
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85068874617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068874617&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2019.109701
DO - 10.1016/j.pnpbp.2019.109701
M3 - Article
C2 - 31299274
AN - SCOPUS:85068874617
VL - 95
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
M1 - 109701
ER -