Susceptibility and resistance of rats to stress-induced decreases in swim-test activity: a selective breeding study.
In this study, selective breeding was used to generate two populations of rats that differed in their susceptibility to showing decreased struggling activity in a swim test after being exposed to uncontrollable electric tail-shock. After five generations of selective breeding, we obtained a population that displayed large decreases in swim-test struggling after shock (swim-test susceptible) and a population that displayed no decrease in struggling after shock (swim-test resistant). Males of this fifth generation from the two selectively-bred populations were then compared for differences in non-swim behavioral measures (home-cage 24-h spontaneous ambulatory activity and food/water intake) and several aspects of brain catecholaminergic activity, including electrophysiological activity of locus coeruleus (LC) neurons, catecholamine/metabolite concentrations in various brain regions, and in vivo tyrosine hydroxylase activity. Interestingly, swim-test resistant rats displayed larger decreases in home-cage ambulatory activity and water intake after exposure to shock than did swim-test susceptible animals. Marked differences were also seen in measures of brain noradrenergic activity. Compared to the susceptible rats, resistant rats showed higher levels of evoked activity of LC neurons, larger shock-induced depletions of norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the LC, lower in vivo tyrosine hydroxylase (TH) activity in ventral bundle projection areas such as the hypothalamus, and larger amounts of NE in dorsal bundle projection areas. Finally, swim-test resistant rats had much higher concentrations of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in striatum and nucleus accumbens than susceptible rats. These results appear to be explainable on the basis that differences in swim-test struggling behavior for which the two populations were selectively bred were a consequence of differences in forebrain DA whereas stress-induced differences in other behavioral measures (i.e. spontaneous ambulation and intake) occurred because swim-test resistant animals showed greater disturbance of the LC-NE system after uncontrollable shock.
Scott
P A
PA
Department of Pharmacology, University of Texas Health Science Center at San Antonio, USA.
Cierpial
M A
MA
Kilts
C D
CD
Weiss
J M
JM
D000818:Animals; D001947:Breeding; D002395:Catecholamines / Q000378:metabolism; D003863:Depression / Q000503:physiopathology*; D004198:Disease Susceptibility; D005260:Female; D007031:Hypothalamus / Q000201:enzymology / Q000502:physiology; D008125:Locus Coeruleus / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012641:Selection, Genetic; D013312:Stress, Physiological / Q000503:physiopathology*; D013550:Swimming / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D002395:Catecholamines; D008734:Methoxyhydroxyphenylglycol; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine