Depressive behaviors

Electrical stimulation in the vicinity of the raphe nuclei has been reported to produce depressant effects on MSRs (32,142). These depressant effects could be attributed to activation of postsynaptic inhibitory receptors analogous to those characterized in the forebrain, except for the fact that the depression was blocked by 5-HT antagonists. The effectiveness of the antagonists suggests that the receptor is more akin to the excitatory 5-HT receptor characterized on motoneurons (134,184). The depressant behavioral effects could result from... 

Some of the depressant behavioral effects of hallucinogens may involve inhibitory postsynaptic 5-HT receptors. For example, depressant effects of hallucinogens on startle and locomotor activity may result from activation of these receptors, since 5-HT itself has similar effects. Studies on supersensitivity are lacking, however, and, again, the absence of selective antagonists prevents definitive conclusions. 

Oral gavage of rat pups with 14mg/kg/day ftom posmatal day 5 through 20 caused reductions in serum thyroxine levels that correlated with depressed behavioral parameters. Further studies using the same protocol reported decreased cell proliferation in the cerebellum and forebrain on postnatal days 11 and 21, respectively. In yet another study, 14mg/day of chlorine dioxide on posmatal days 1-20 was associated with some neurotoxicity (decreased forebrain weight and reduced synapse formation on day 35), but the neurotoxicity was not correlated with any antithyroid activity of this chemical. ... 

Pare, WJ., Redei, E. Depressive behavior and stress ulcer in Wistar Kyoto rats. J. Physiol 87, 229-238, 1993. 

Much evidence supports the neurotrophic hypothesis of depression, but not all evidence is consistent with this concept. Animal studies in BDNF knockout mice have not always suggested an increase in depressive or anxious behaviors that would be expected with a deficiency of BDNF. In addition, some animal studies have found an increase in BDNF levels after some types of social stress and an increase rather than a decrease in depressive behaviors with lateral ventricle injections of BDNF. 

A proposed explanation for the discrepant findings on the role of neurotrophic factors in depression is that there are polymorphisms for BDNF that may yield very different effects. Mutations in the BDNF gene have been found to be associated with altered anxiety and depressive behavior in both animal and human studies. 

Although there is evidence that A3AR ko mice are more prone to depressive behavior, it is also reported that they have increased performance in the elevated-plus maze and light/dark box suggestive of reduced anxiety but this is most probably a consequence of the increase in exploratory activity due to increased motor activity (Fedorova et al. 2003). 

Feng P and Ma Y. Clomipramine suppresses postnatal REM sleep without increasing wakefulness implications for the production of depressive behavior. Sleep 2002 25 177-184. 

Indeed, there is a correlation between impaired NE transmission and depressive behavior. Postmortem studies demonstrated increased NE levels in the brains of unipolar and bipolar suicide victims (Juckel et al., 2000 Wiste et al., 2008). One positron emission tomography (PET) study suggested that depressive patients have an increased activity of MAO-A, which might result in reduced catecholamine levels (Meyer et al., 2006). Another imaging study showed correlation between the degree of loss of limbic NE innervation and severity of depressive symptoms in Parkinson patients (Brooks and Piccini 2006 Remy et al., 2005). 

Topiramate has been associated with several psychiatric adverse events, such as nervousness, depression, behavioral problems, mood lability, and psychosis. Obsessive-compulsive disorder has also been reported (650). 

One in every 1,000 people in the United States currently receives lithium, as Li2C03, for the treatment and prophylaxis of manic-depressive behavior. Doses of 250 mg to 2 g per day are administered in order to maintain a 0.5 to 2.0 mM concentration window, outside of which the drug is either toxic or ineffective. The detailed molecular mechanism by which Li ion brings about its remarkable chemotherapeutic effects is largely unknown, but there are various theories. One theory proposes that lithium binds to inositol phosphates, inhibiting their breakdown to inositol, and so reducing inositol-containing phospholipids. A consequence of this chain of events would be disruption of the neurotransmis-... 

J. Greist, M. Klein, et al., Antidepressant Running Running as Treatment for Nonpsychotic Depression. Behavioral Medicine 5 (1978) 19-24. 

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