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Flinders resistant hypocholinergic rats exhibit startle sensitization and reduced startle thresholds
A Markou1, K Matthews, D H Overstreet
1Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Abstract:
Based on the hypothesis that depression involves a cholinergic-adrenergic neurotransmitter imbalance, a putative genetic animal model of depression has been developed by selectively breeding rats to exhibit hypocholinergia (Flinders Resistant Line--FRL), or hypercholinergia (Flinders Sensitive Line--FSL). The present experiments were designed to test the behavioral reactivity of these rats to external stimuli by measuring acoustic startle responses. The FRL rats exhibited lower startle thresholds compared to both FSL and control rats, while the FSL rats' startle thresholds were between those of controls and FRL rats. Despite the differences in thresholds, the three groups demonstrated similar levels of maximal startle reactivity to a high-intensity acoustic stimulus. With repeated stimulus presentations, FRL rats developed startle sensitization, a rarely observed phenomenon, while FSL and control rats exhibited habituation. There were no differences between the three groups in prepulse inhibition of startle. These results indicated that FRL rats exhibited interesting startle phenomena that are characteristic of certain psychiatric disorders, such as schizophrenia, post-traumatic stress disorder, and, potentially, depression.
Insights
Genetic animal models of depression show distinct acoustic startle responses. Flinders Resistant Line rats exhibited lower startle thresholds and sensitization, unlike Flinders Sensitive Line and control rats.
Area of Science:
- Neuroscience
- Behavioral Genetics
- Psychiatry
Background:
- Depression is hypothesized to involve a cholinergic-adrenergic neurotransmitter imbalance.
- Genetic animal models, Flinders Resistant Line (FRL) and Flinders Sensitive Line (FSL) rats, were developed to study this imbalance.
- These models exhibit hypocholinergia (FRL) or hypercholinergia (FSL).
Purpose of the Study:
- To investigate the behavioral reactivity of FRL and FSL rats to external stimuli.
- To measure acoustic startle responses as an indicator of behavioral reactivity.
- To compare startle response patterns between genetically distinct rat lines and controls.
Main Methods:
- Selective breeding of rats to create hypocholinergic (FRL) and hypercholinergic (FSL) lines.
- Measurement of acoustic startle responses to auditory stimuli.
- Assessment of startle thresholds, maximal reactivity, sensitization, habituation, and prepulse inhibition.
Main Results:
- FRL rats showed significantly lower acoustic startle thresholds compared to FSL and control rats.
- FSL rats displayed startle thresholds intermediate between FRL and control rats.
- FRL rats exhibited startle sensitization with repeated stimuli, while FSL and control rats showed habituation.
- No group differences were observed in maximal startle reactivity or prepulse inhibition.
Conclusions:
- The Flinders Resistant Line rats display unique startle response patterns, including sensitization.
- These startle phenomena in FRL rats resemble those observed in certain psychiatric disorders like schizophrenia, PTSD, and potentially depression.
- The study supports the utility of these genetic models in investigating the neurobiological underpinnings of depression and related disorders.