| 1 | Neuropeptides 2008 Jun 42: 301-9 |
|---|---|
| PMID | 18359517 |
| Title | Effect of D(3) dopamine receptors blockade on the cognitive effects of angiotensin IV in rats. |
| Abstract | Our previous studies showed that D(1) and D(2) dopamine receptors are indispensable for the cognitive effects of ANGiotensin IV (ANG IV) and its des-Phe(6) derivative des-Phe(6)-ANG IV to occur. As most neuroleptics currently used in the treatment of schizophrenia have variable D(2)/D(3) dopaminolytic selectivity, in this study we searched for the role of the D(3) dopamine receptors in facilitating learning and improving memory actions of ANG IV and des-Phe(6)-ANG IV in rats. For this purpose, we evaluated the recall of the passive avoidance (PA) behaviour, object recognition (OR) memory, and the spatial working memory (WM) in rats treated with the intraperitoneal (i.p.) nafadotride (N[(n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyanonaphtalene-2-carboxamide), a highly selective D(3) receptor blocker and then by an intracerebroventricular (i.c.v.) ANG IV or des-Phe(6)-ANG IV. Separate groups of rats receiving the same treatments were run to check for the possible participation of unspecific motor (open field) or emotioned (elevated "plus" maze) effects of our treatments in the results of the cognitive tests. The results revealed ANG IV to express its improving recall of PA, OR memory and WM action roughly similarly in all groups showing only minor or null significance of the D(3) receptors blockade. Interestingly, in the nafadotride pretreated rats, des-Phe(6)-ANG IV beneficial effect on the recall of the PA was weaker than that of ANG IV. Improvement of the spatial WM in an eight-arm radial maze, similar after ANG IV and des-Phe(6)-ANG IV, was not significantly affected by nafadotride. There were no motor and only minor anxiogenic effects of ANG IV and des-Phe(6)-ANG IV abolished by nafadotride in the former case. In conclusion, this study points to the minor significance of the D(3) dopamine receptors in the cognitive effects of ANG IV and to the interesting, though unexplained, inhibition by nafadotride of the des-Phe(6)-ANG IV effects. |
| SCZ Keywords | schizophrenia |
| 2 | Pharmacol Rep 2014 Jun 66: 436-41 |
| PMID | 24905520 |
| Title | Telmisartan attenuates cognitive impairment caused by chronic stress in rats. |
| Abstract | The potential effect of chronic treatment with telmisartan, an ANGiotensin type 1 receptor blocker (ARB) and partial agonist of peroxisome proliferator--activated receptor ? (PPAR?), on stress-related disorders is a matter of considerable interest. The existing data suggest that ANGiotensin II (ANG II) plays a major role in exaggerated sympathetic and hormonal response to stress. Enhanced formation of ANG II and increased AT1 receptor activity is associated with devastating impact of stress on central nervous system, which may trigger many psychiatric disorders such as depression, schizophrenia or post-traumatic stress disorder. Some of the anti-stress effects of ARBs have already been proven but these on the stress-induced cognitive impairment were examined only for candesartan. In this study, we tested a hypothesis that blockade of stress response by another ARB telmisartan alleviates the negative effect of prolonged restraint stress on cognitive functions of male Wistar rats. The preventive action of long-lasting treatment with telmisartan (1mg/kg body weight) against impairment caused by chronic stress (2h daily for 21 days) on recall was evaluated in a passive avoidance (PA) situation and object recognition test (ORT). Locomotor activity and anxiety behavior were tested respectively, in an open field and an elevated plus-maze. The results of this study indicate that telmisartan diminishes deleterious effects of chronic restraint stress on memory in a statistically significant manner (p<0.01) in both, PA situation and ORT. It appears that telmisartan may constitute a new therapeutic option in a stress-related cognitive impairment. |
| SCZ Keywords | schizophrenia |
| 3 | Psychiatry Res 2015 Oct 229: 702-7 |
| PMID | 26296754 |
| Title | Angiotensin converting enzyme activity is positively associated with IL-17a levels in patients with schizophrenia. |
| Abstract | Previous studies of our group showed increased plasmatic ANGiotensin-I Converting Enzyme (ACE) activity in schizophrenia (SCZ) patients compared to healthy controls, which was also associated to poor cognitive functioning. The ACE main product ANGiotensin II (ANG-II) has pro-inflammatory properties. Activated immune-inflammatory responses in SCZ and their association with disease progression and cognitive impairments are also well-described. Therefore, we examined here the association of plasma ACE activity and inflammatory mediators in 33 SCZ patients and 92 healthy controls. Non-parametric correlations were used to investigate the association of the enzyme activity and the peripheral levels of immune inflammatory markers as interleukins, tumor necrosis factor (TNF-?), and interferon (IFN-?). Although no significant correlations could be observed for ACE activity and measured cytokines levels in healthy controls, a significant positive correlation for ACE enzymatic activity and IL-17a levels was observed in SCZ patients. Correcting for gender did not chANGe these results. Moreover, a significant association for ACE activity and IFN-? levels was also observed. To our knowledge, this is the first study to show a significant association between higher ACE activity and the levels of cytokines, namely IL-17a and IFN-?, in patients with SCZ. |
| SCZ Keywords | schizophrenia |