Impaired contextual fear-conditioning in MAM rodent model of schizophrenia
| Autor: | Kathryn M. Gill, Anthony A. Grace, Sarah A. Miller |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
Methylazoxymethanol Acetate Time Factors Conditioning Classical Neurotoxins Action Potentials Context (language use) Hippocampal formation Article Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dopamine Pregnancy medicine Animals Fear conditioning Amphetamine Biological Psychiatry Fear processing in the brain Methylazoxymethanol acetate Learning Disabilities Dopaminergic Neurons Ventral Tegmental Area Fear 030227 psychiatry Rats Apomorphine Psychiatry and Mental health Disease Models Animal chemistry Prenatal Exposure Delayed Effects Schizophrenia Central Nervous System Stimulants Female Psychology Neuroscience 030217 neurology & neurosurgery Locomotion medicine.drug |
| Popis: | The methylazoxymethanol acetate (MAM) rodent neurodevelopmental model of schizophrenia exhibits aberrant dopamine system activation attributed to hippocampal dysfunction. Context discrimination is a component of numerous behavioral and cognitive functions and relies on intact hippocampal processing. The present study explored context processing behaviors, along with dopamine system activation, during fear learning in the MAM model. Male offspring of dams treated with MAM (20mg/kg,i.p.) or saline on gestational day 17 were used for electrophysiological and behavioral experiments. Animals were tested on the immediate shock fear conditioning paradigm, with either different preconditioning contexts or varying amounts of context pre-exposure (0–10 sessions). Amphetamine-induced locomotor activity and dopamine neural activity was measured 1-week after fear conditioning. Saline, but not MAM animals, demonstrated enhanced fear responses following a single context pre-exposure in the conditioning context. One week following fear learning, saline rats with 2 or 7 minutes of context pre-exposure prior to fear conditioning also demonstrated enhanced amphetamine-induced locomotor response relative to MAM animals. Dopamine neuron recordings showed fear learning-induced reductions in spontaneous dopamine neural activity in MAM rats that was further reduced by amphetamine. Apomorphine administration confirmed that reductions in dopamine neuron activity in MAM animals resulted from over excitation, or depolarization block. These data show a behavioral insensitivity to contextual stimuli in MAM rats that coincides with a less dynamic dopamine response after fear learning. |
| Databáze: | OpenAIRE |
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