Progress in neuro-psychopharmacology & biological psychiatry
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jun 2011
ReviewMelatonin agonists in primary insomnia and depression-associated insomnia: are they superior to sedative-hypnotics?
Current pharmacological treatment of insomnia involves the use of sedative-hypnotic benzodiazepine and non-benzodiazepine drugs. Although benzodiazepines improve sleep, their multiple adverse effects hamper their application. Adverse effects include impairment of memory and cognitive functions, next-day hangover and dependence. ⋯ The novel antidepressant agomelatine, a dual action agent with affinity for melatonin MT1 and MT2 receptors and 5-HT2c antagonistic properties, constitutes a new approach to the treatment of major depressive disorders. Agomelatine ameliorates the symptoms of depression and improves the quality and efficiency of sleep. Taken together, the evidence indicates that MT1/MT2 receptor agonists like ramelteon or agomelatine may be valuable pharmacological tools for insomnia and for depression-associated insomnia.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jun 2011
ReviewThe WAG/Rij strain: a genetic animal model of absence epilepsy with comorbidity of depression [corrected].
A great number of clinical observations show a relationship between epilepsy and depression. Idiopathic generalized epilepsy, including absence epilepsy, has a genetic basis. The review provides evidence that WAG/Rij rats can be regarded as a valid genetic animal model of absence epilepsy with comorbidity of depression. ⋯ Whether the neurochemical changes are primary to depression-like behavioral alterations remains to be determined. In conclusion, the WAG/Rij rats can be considered as a genetic animal model for absence epilepsy with comorbidity of dysthymia. This model can be used to investigate etiology, pathogenic mechanisms and treatment of a psychiatric comorbidity, such as depression in absence epilepsy, to reveal putative genes contributing to comorbid depressive disorder, and to screen novel psychotropic drugs with a selective and/or complex (dual) action on both pathologies.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jun 2011
Comorbid obsessive-compulsive personality disorder in obsessive-compulsive disorder (OCD): a marker of severity.
Comorbid obsessive-compulsive personality disorder (OCPD) is well-described in obsessive-compulsive disorder (OCD). It remains unclear, however, whether OCPD in OCD represents a distinct subtype of OCD or whether it is simply a marker of severity in OCD. ⋯ The majority of our findings suggest that in OCD, patients with OCPD do not have a highly distinctive phenomenological or genetic profile, but rather that OCPD represents a marker of severity.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jun 2011
Peripheral administration of NR2 antagonists attenuates orofacial formalin-induced nociceptive behavior in rats.
The present study investigated the role of the peripheral NR2 subunits of N-methyl-d-aspartatic acid (NMDA) receptors in inflammatory orofacial pain. Experiments were carried out using adult male Sprague-Dawley rats weighing 220 to 280 g. Formalin (5%, 50 μl) was applied subcutaneously to the vibrissa pad. ⋯ The antinociceptive doses of memantine (200 μg), 5,7-dichlorokynurenic acid (25 μg), AP-5 (20 μg), PPPA (2.5 μg), or Ro 25-6981 (50 μg) injected into the contralateral hind paw did not affect the number of scratches in both the first and second phases. Moreover, the peripheral administration of NR2 subunit antagonists, including other NMDA receptor blockers, did not produce any motor dysfunction. These results indicate that a targeted blockade of peripheral NR2 receptors is a potentially important new method of treating inflammatory pain in the orofacial area.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Apr 2011
ReviewThe new '5-HT' hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression.
This paper reviews the body of evidence that not only tryptophan and consequent 5-HT depletion, but also induction of indoleamine 2,3-dioxygenase (IDO) and the detrimental effects of tryptophan catabolites (TRYCATs) play a role in the pathophysiology of depression. IDO is induced by interferon (IFN)γ, interleukin-6 and tumor necrosis factor-α, lipopolysaccharides and oxidative stress, factors that play a role in the pathophysiology of depression. TRYCATs, like kynurenine and quinolinic acid, are depressogenic and anxiogenic; activate oxidative pathways; cause mitochondrial dysfunctions; and have neuroexcitatory and neurotoxic effects that may lead to neurodegeneration. ⋯ It is concluded that activation of the TRYCAT pathway by IDO and TDO may be associated with the development of depressive symptoms through tryptophan depletion and the detrimental effects of TRYCATs. Therefore, the TRYCAT pathway should be a new drug target in depression. Direct inhibitors of IDO are less likely to be useful drugs than agents, such as kynurenine hydroxylase inhibitors; drugs which block the primary immune response; compounds that increase the protective effects of kynurenic acid; and specific antioxidants that target IDO activation, the immune and oxidative pathways, and 5-HT as well.