Isolated studies have produced empirically unconnected observations about endogenous depression and REM sleep. Our objective is to connect these observations by a web of related experiments on the same individuals. This is best done in animals. Our start is work on validity of a new animal model of endogenous depression and its treatment. Improvement of human endogenous depression by imipramine correlates with improvement in REM depriving awakenings and improvement by either correlates with posttreatment REM rebound. In animals REM depriving awakenings increase behaviors that are decreased in human endogenous depression. This suggests that animal Behavioral Activation may model a human antidepressant process.
Our specific aims are tests of whether in rats, as in endogenous depressives, Behavioral Activation by either REM deprivation or imipramine will correlate with Behavioral Activation by the other treatment and with posttreatment REM rebound. In rats postnatal REM deprivation produces adults with some behavioral and REM sleep abnormalities of endogenous depression. The adult rats may model endogenous depression.
Our specific aims are to test whether the adult rats will have other behavioral and REM sleep abnormalities of endogenous depression and its treatment responses (Behavioral Activation with antidepressant treatments). In rats brief REM deprivation has delayed effects. Weeks later, motor responses to antidepressant drugs are increased, suggesting that interrupted treatment may be more efficacious than continuous treatment.
Our specific aim i s to test the hypothesis that a second brief course of REM depriving, antidepressant treatments, weeks after a first course, will activate rat behaviors more than a first course. If successful, our animal models of endogenous depression and its treatment would have broad validity: many behavioral, REM sleep, and treatment characteristics of endogenous depression. The model could be used to study brain processes in depression and its treatment, screen new treatments, improve therapeutic efficacy, and both confirm and expand the matrix of variables concerned with endogenous depression.

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National Institute of Mental Health (NIMH)
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Emory University
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Feng, P; Ma, Y; Vogel, G W (2001) Ontogeny of REM rebound in postnatal rats. Sleep 24:645-53
Vogel, G W; Feng, P; Kinney, G G (2000) Ontogeny of REM sleep in rats: possible implications for endogenous depression. Physiol Behav 68:453-61
Kinney, G G; Vogel, G W; Feng, P (1998) Brainstem carbachol injections in the urethane anesthetized rat produce hippocampal theta rhythm and cortical desynchronization: a comparison of pedunculopontine tegmental versus nucleus pontis oralis injections. Brain Res 809:307-13
Kinney, G G; Vogel, G W; Feng, P (1997) Decreased dorsal raphe nucleus neuronal activity in adult chloral hydrate anesthetized rats following neonatal clomipramine treatment: implications for endogenous depression. Brain Res 756:68-75
Vogel, G; Hagler, M (1996) Effects of neonatally administered iprindole on adult behaviors of rats. Pharmacol Biochem Behav 55:157-61
Vogel, G; Hagler, M; Hennessey, A et al. (1996) Dose-dependent decrements in adult male rat sexual behavior after neonatal clorimipramine treatment. Pharmacol Biochem Behav 54:605-9
Rosenthal, M S; Vogel, G W (1994) The effects of a 3-day increase of ambient temperature on body temperature and REM sleep in an animal model of depression. Sleep 17:291-7
Rosenthal, M S; Vogel, G W (1993) The effect of a 3-day increase of ambient temperature toward the thermoneutral zone on rapid eye movement sleep in the rat. Sleep 16:702-5
Yavari, P; Vogel, G W; Neill, D B (1993) Decreased raphe unit activity in a rat model of endogenous depression. Brain Res 611:31-6
Hartley, P; Neill, D; Hagler, M et al. (1990) Procedure- and age-dependent hyperactivity in a new animal model of endogenous depression. Neurosci Biobehav Rev 14:69-72

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