Flinders resistant hypocholinergic rats exhibit startle sensitization and reduced startle thresholds.
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.
Markou
A
A
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Matthews
K
K
Overstreet
D H
DH
Koob
G F
GF
Geyer
M A
MA
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D005260:Female; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000502:physiology; D007531:Isoflurophate / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D013216:Reflex, Startle / Q000502:physiology*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology
D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D007531:Isoflurophate; D000109:Acetylcholine