RESUMEN
In 1982 our laboratory proposed a new animal model of endogenous depression. The proposal was that in rats, neonatally administered clomipramine (CLI) will produce adult animals that model endogenous depression. We summarize here several tests of the validity of the model. Results were that after neonatal CLI, adult male rats showed behavioral abnormalities of the human disorder: decreased sexual, aggressive, and intracranial self-stimulation activities, as well as motor hyperactivity in a stressful situation. Preliminary evidence suggested that behavioral abnormalities in rats (sexual, aggressive, and motor) briefly treated with antidepressant treatments (imipramine, REM sleep deprivation) begin to normalize. Lastly, after neonatal CLI, the adult rats showed REM sleep abnormalities of endogenous depression, viz, low REM latency, frequent sleep onset REM periods, and abnormal temporal course of REM rebound after REM sleep deprivation. These results supported the hypothesis that in rats neonatal CLI produced adult animals that modelled endogenous depression.
Asunto(s)
Trastorno Depresivo/fisiopatología , Sueño/fisiología , Animales , Masculino , Ratas , Ratas EndogámicasRESUMEN
We have replicated the findings of Mirmiran and colleagues that neonatal administration of the antidepressant clomipramine (CLI) to male rats results in hyperactivity in open-field tests in adulthood. We report that this effect does not reliably occur in a "Digiscan" activity device. The difference in effect between the two activity measuring devices may be due to more stress being present in the open-field test, and we propose that the CLI-treated rats may be more reactive to stress. This hypothesized enhanced reactivity to stress may be similar to the proposed vulnerability of depressed humans to stress. In addition, we have found that the open-field effect does not occur until the rats are at least 4 months old; this delayed effect may be analogous to the progressive onset of endogenous depression in humans.
Asunto(s)
Envejecimiento/fisiología , Trastorno Depresivo/fisiopatología , Hipercinesia/inducido químicamente , Animales , Antidepresivos/farmacología , Clomipramina , Modelos Animales de Enfermedad , Hipercinesia/fisiopatología , Masculino , Ratas , Ratas Endogámicas , Estrés Psicológico/fisiopatologíaRESUMEN
Neonatal treatment of rats with clomipramine may produce adult animals which model endogenous depression. We report here that a major factor of depression in humans, the diminished capacity for pleasure, appears present in these rats. At age 7 months, bar-press responding for rewarding hypothalamic stimulation is reduced across a range of intensities. At age 4 or 5 months this effect is not seen, although other behavioral abnormalities are present at the younger age. The delayed onset of diminished intracranial self-stimulation may relate to the gradual insidious onset of endogenous depression in humans.
Asunto(s)
Trastorno Depresivo/fisiopatología , Hipotálamo/fisiopatología , Autoestimulación/fisiología , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas EndogámicasRESUMEN
Our laboratory has proposed a new animal model of endogenous depression. The proposal is that in rats neonatal clomipramine (CLI) produces adult animals that model endogenous depression. Diminished sexual activity is a salient behavioral abnormality found in endogenous depression. This suggests that an animal model of endogenous depression should show diminished sexual activity. We report here a test of the prediction that after neonatal treatment with CLI, adult male rats show decreased sexual activity. We found that after neonatal CLI, adult male Long-Evans rats had a pervasive diminution of sexual activities including decreased mounts, intromissions, ejaculations, and increased mount latencies and postejaculatory pause. Sprague-Dawley and Wistar strains also tended to show decreased intromissions and ejaculations, but their baseline sexual activity was too low to give interpretable data. The results with the sexually active Long-Evans strain are consistent with the hypothesis that neonatal CLI produces adult rats that model human endogenous depression.
Asunto(s)
Clomipramina , Trastorno Depresivo/fisiopatología , Conducta Sexual Animal/fisiología , Animales , Trastorno Depresivo/inducido químicamente , Modelos Animales de Enfermedad , Ratas , Ratas Endogámicas , Conducta Sexual Animal/efectos de los fármacos , Especificidad de la EspecieRESUMEN
Endogenous depression has reliable REM sleep abnormalities. These include a short REM latency, frequent sleep onset REM periods, and after REM sleep deprivation (RSD), an abnormal temporal course of REM rebound in the presence of a normal total REM rebound. The reliability of these abnormalities suggests that they ought to be present in an animal model of endogenous depression. In 1982, we proposed a new animal model of endogenous depression. Our hypothesis is that in rats neonatal clomipramine (CLI) will produce adult animals that model endogenous depression. In this study we tested the prediction that after neonatal treatment with CLI, adult rats will show the above three REM sleep abnormalities of human endogenous depression. We found that neonatal treatment with CLI produced rats that at age 6 months had shorter REM latency, more sleep onset REM periods than control rats, and after RSD, had an abnormal temporal course of REM rebound in the presence of a normal total REM rebound. The finding of these REM sleep abnormalities supported the validity of the animal model of endogenous depression.
Asunto(s)
Clomipramina/farmacología , Trastorno Depresivo/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Sueño REM/fisiología , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas EndogámicasRESUMEN
Clomipramine, administered to neonatal rats, has been reported to produce adult behavioral and REM sleep abnormalities. They include decreased sexual behavior, increased ambulation in the outer part of an open-field arena, increased REM sleep % of total sleep time, and in descriptive data, short REM latency, and increased REM phasic events. Since these abnormalities resemble some found in human endogenous depression, we have hypothesized that the adult rats represent an animal model of depression. Diminished aggressive behavior is a common characteristic of endogenous depression. This study tested the validity of the animal depression model by determining in rats the effect of neonatal clomipramine on adult shock-induced fighting. Experimental rats were treated neonatally with clomipramine and control rats were treated neonatally with saline. When they matured, compared with control rats, experimental rats had significantly fewer offensive fighting responses, and significantly more defensive fighting responses. The findings add some support to the validity of the animal depression model produced by neonatal clomipramine.