On the Existence and Function of Galanin Receptor Heteromers in the Central Nervous System.

On the existence and function of galanin receptor heteromers in the central nervous system.

Filed under: Depression Treatment

Front Endocrinol (Lausanne). 2012; 3: 127
Fuxe K, Borroto-Escuela DO, Romero-Fernandez W, Tarakanov AO, Calvo F, Garriga P, Tena M, Narvaez M, Millón C, Parrado C, Ciruela F, Agnati LF, Narvaez JA, Díaz-Cabiale Z

Galanin receptor (GalR) subtypes 1-3 linked to central galanin neurons may form heteromers with each other and other types of G protein-coupled receptors in the central nervous system (CNS). These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15) to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1-5-HT1A heteromers in cellular models with trans-inhibition of the protomer signaling. A GalR1-GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15) in the CNS. Furthermore, a GalR1-GalR2-5-HT1A heterotrimer is postulated to explain why only galanin (1-15) but not galanin (1-29) can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR-5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR-NPYY1 receptor interactions in putative GalR-NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1-GalR2 heteromer) appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1-GalR2-NPYY2 heterotrimer. Finally, putative GalR-?2-adrenoreceptor heteromers with antagonistic receptor-receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression.
HubMed – depression

Attitudes Toward Assisted Suicide and Life-Prolonging Measures in Swiss ALS Patients and Their Caregivers.

Filed under: Depression Treatment

Front Psychol. 2012; 3: 443
Stutzki R, Schneider U, Reiter-Theil S, Weber M

Objectives: In Switzerland, assisted suicide (AS) is legal, provided that the person seeking assistance has decisional capacity and the person assisting is not motivated by reasons of self-interest. However, in this particular setting nothing is known about patients’ and their caregivers’ attitudes toward AS and life-prolonging measures. Methods: Data was retrieved through validated questionnaires and personal interviews in 33 patients and their caregivers covering the following domains: physical function according to the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), demographic data, quality of life, anxiety, depression, social situation, spirituality, burden of disease, life-prolonging, and life-shortening acts. Results: In patients the median time after diagnosis was 9?months (2-90) and the median Amyotrophic Lateral Sclerosis (ALS) FRS-R score was 37 (22-48). The majority of patients (94%; n?=?31) had no desire to hasten death. Patients’ and caregivers’ attitudes toward Percutaneous Endoscopic Gastrostomy (PEG) and Non-Invasive Ventilation (NIV) differed. Significantly more patients than caregivers (21.2 versus 3.1%) stated that they were against NIV (p?=?0.049) and against PEG (27.3 versus 3.1%; p?=?0.031). Answers regarding tracheotomy were not significantly different (p?=?0.139). Caregivers scored significantly higher levels of “suffering” (p?=?0.007), “loneliness” (p?=?0.006), and “emotional distress” answering the questionnaires (p?HubMed – depression

Antidepressant-like activity of (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a), a novel 5-HT(3) receptor antagonist: An investigation in behaviour-based rodent models of depression.

Filed under: Depression Treatment

Indian J Pharmacol. 2012 Sep; 44(5): 560-5
Mahesh R, Kumar B, Jindal A, Bhatt S, Devadoss T, Pandey DK

The present study was designed to investigate the antidepressant potential of (4-phenylpiperazin-1-yl) (quinoxalin-3-yl) methanone (4a), a novel 5-HT(3) receptor antagonist, with an optimal log P (2.84) and pA(2) value (7.3) greater than ondansetron (6.9) using rodent behavioural models of depression.Swiss albino mice were used in actophotometer test, forced swim test (FST) and 5-hydroxytryptophan (5-HTP) induced head twitch response. Reserpine induced hypothermia (RIH) and olfactory bulbectomy were performed in male Wistar rats. Statistical analysis was carried out by using one-way analysis of variance followed by Tukey’s test.Acute treatment of 4a (1-4 mg/kg, i.p.) in mice produced antidepressant-like effects in FST without affecting the baseline locomotion in actophotometer test. Further, 4a (2-4 mg/kg, i.p.) potentiated the 5-HTP induced head twitches response in mice and also antagonized RIH in rats. Furthermore, sub-chronic (14 days) treatment with 4a (2-4 mg/ kg, p.o.) significantly attenuated the behavioural anomalies induced by bilateral olfactory bulbectomy in rats in modified open field exploration.These preliminary investigations confirm that 4a exhibits antidepressant-like activity in behaviour based rodent models of depression.
HubMed – depression

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