Anxiolytic-like effects of nociceptin/orphanin FQ in the elevated plus maze and in the conditioned defensive burying test in rats.

Different reports suggest that nociceptin/orphanin FQ (N/OFQ) may have either anxiolytic- or anxiogenic-like effect in rodents. Since N/OFQ elicits hypolocomotion, which undergoes rapid tolerance, and hypolocomotion may be associated to emotional consequences, the present study was designed to investigate the effect of N/OFQ on anxiety after development of tolerance to its hypolocomotor effect. The effect of single or double intracerebroventricular (i.c.v.) injection of N/OFQ was evaluated on anxiety-related behaviors in rats, in the elevated plus maze (EPM) and conditioned defensive burying (CDB) tests. After single administration, N/OFQ displayed an anxiogenic-like pattern of response on the elevated plus maze but hypolocomotion was also observed. Conversely, in the CDB test, N/OFQ induced a clear-cut anxiolytic pattern. To produce tolerance to N/OFQ-induced hypolocomotion the peptide was administered by two i.c.v. injections separated by 120 min; in these conditions it decreased the expression of anxiety-related behaviors in both tests without affecting locomotor activity. The nociceptin/orphanin FQ peptide (NOP) receptor antagonist UFP-101 significantly reduced the effects of N/OFQ to control values in either tests. Corticosterone levels were significantly increased after a single N/OFQ administration (not in a dose-dependent manner) but this increase did not reach significance after double administration (1 nmol/rat). Our results support the idea that N/OFQ may act as an anxiolytic-like agent in the rat; the apparent anxiogenic-like effect observed following its single administration in the EPM may be consequent to its effect on locomotion.

Acute noise stress analgesia in relation to 5-HT2 and mu-opioid receptor changes in the frontal cortex of young mice.

A number of studies have reported that exposure to stress provoked behavioural changes, including analgesia, in rodents. Differences have been observed in these responses to different types of stress and a link between hormones and neurotransmitters proposed. We studied the effect of acute noise stress on nociception and the possible changes in the serotonergic and opioidergic systems in young mice of both sexes. Naloxone pre-treatment was also investigated. Noise stress was produced by a sound source, nociception was measured by the hot-plate test and binding characteristics were evaluated by a radioligand binding technique using membrane preparation from the total frontal cortex. Acute noise stress provoked an antinociceptive effect, associated with an increase in plasma corticosterone levels, a decrease in the number of 5-HT2 receptors in stressed male and female mice and a decrease in the number of mu receptors in both sexes. The behavioural and biochemical effects were antagonized by 1 mg/kg of naloxone. Acute noise stress behaves like other types of stress on nociception. The opioidergic system seems to be involved in this behaviour but also the serotonergic system may play a role. Sex differences were detected in the number of 5-HT2 and mu receptors between male and female mice not subjected to stress, while the percentage decrease in 5-HT2 and mu receptors did not differ significantly between the two sexes.

Effect of oral chronic isoflavones supplementation on male rat sexual performances and sexual hormone plasma levels.

The aim of our study was to evaluate how a chronic isoflavones oral supplementation could affect male rat sexual behavior in relationship to cause eventual change in plasma sexual hormone concentrations. Isoflavones were administered in the form of a standardized dry extract of soybeans. Three groups of 20 sexually experienced male rats were consecutively treated with saline 2 ml, or isoflavones 0.4 mg/kg(-1) or 0.8 mg/kg(-1) soybean dried extract via gastric tube for 40 days. No significant differences were found as regards sexual performances of the three studied groups at the baseline levels nor at the end of the study: in relationship to the base-line value, only mount frequency increased in the control group (z = -2.047, p = 0.041), while intromission frequency in the high dosage isoflavones group (z = -2.484, p = 0.13). At the base-line test 23.08% of rats in each group were not able to conclude their performance in the standard time, while at the end of the study only 15.38% of the control group rats were not able to do this. No significant difference has been observed as regards FSH, progesterone, androstenedione plasma levels, either between groups or between baseline and study end. Slight differences were found regards LH and testosterone plasma level.

[Cardiovascular risk factors in severely ill psychiatric patients]. / Fattori di rischio cardiovascolari in pazienti psichiatrici gravemente malati.

The most recent European guidelines for coronary heart disease (CHD) prevention acknowledges that stress/anxiety and depression are independent risk factors for CHD. The Psychiatric Patients Health Status Study is a transversal study on the health condition of 1.590 serious psychiatric patients. We've built a database containing historical, clinical and laboratory data of the 1.374 subjects aged > 30 years. 25% of them has a family history of CHD and 7% of cerebrovascular disease. 1.4% has clinical history of CHD, while 5.7% has a clinical history of cerebrovascular disease. The 37.3% is cigarette smoker. Moreover, in this population there is a high prevalence of overweighting (M: 25.30%; F: 11.30%) and obese (M: 13.25%; F: 5.82%) subjects. Furthermore, we observed a 40% of hypertensive patients among that only one half with controlled blood pressure level and 6.5% of diabetics or glucose intolerant among that 78% with uncontrolled basal glucose level. Finally, 40% of these subjects is affected by dyslipidaemia and 98% of them has uncontrolled plasma lipid levels. 16% of patients accounts more than one pharmacologically treatable CHD risk factor. A non-lethal CHD event in these patients could really increases the risk of non-compliance and of drug-drug interactions because of the high number of drugs needed to treat both kind of disease. Thus, we find unethical do not treat hypertension, dyslipidemia and diabetes in severe psychiatric patients.

Preprotachykinin A gene expression after administration of 3,4-methylene dioxymethamphetamine (Ecstasy).

This study tested the effects of 8 days of subchronic administration of 3,4-methylene dioxymethamphetamine (MDMA) (5 mg/kg b.w.) on preprotachykinin A mRNA levels in discrete rat brain regions. In situ hybridization examined preprotachykinin A mRNA levels in the core and shell of the nucleus accumbens, the islands of Calleja, the olfactory tubercle, the dorsal and ventral caudate-putamen, the bed nucleus of the stria terminalis, the medial preoptic area, the medial habenular nucleus and in the postero-dorsal part of the medial amygdala. Higher levels of preprotachykinin A mRNA were found in the core and shell of the nucleus accumbens, in the islands of calleja, in the olfactory tubercle, in the bed nucleus of the stria terminalis, in the medial habenular nucleus and the postero-dorsal part of the medial amygdala, compared to control animals. Conversely, increased preprotachykinin A mRNA levels were observed in the dorsal and ventral caudate-putamen in MDMA treated when compared to control rats. In the social memory test, MDMA significantly impaired rats' short-term working memory. These results show that chronic exposure to MDMA strongly affects preprotachykinin A mRNA levels in discrete rat brain regions. These changes occur in experimental conditions in which working memory is markedly reduced, suggesting that changes in gene expression of tachykinin mechanisms may contribute to the effects of MDMA on memory function.