PURPOSE: Anabolic androgenic steroids (AASs) are synthetic androgen-like compounds which are abused in sport communities despite their side effects. Nerve growth factor (NGF) influences neuronal differentiation and survival, and also mediates higher brain functions such as learning and memory. Changes in NGF expression have been implicated in neurodegenerative disorders, including Alzheimer's disease. Hence, we decided to study the effect of chronic AASs exposure on brain NGF profile, NGF-dependent cholinergic function and related behavioral performance. METHODS: Male Wistar rats were injected for 4 weeks with either nandrolone or stanozolol at daily doses (5.0 mg/kg, s.c.) that are considered equivalent to those abused by humans. NGF levels and NGF receptor (TrkA and p75NTR) expression were measured in the hippocampus and in the basal forebrain. Choline acetyltransferase expression was evaluated in basal forebrain. Spatial learning and memory were assessed using the Morris water maze. RESULTS: AASs treatment caused region-specific changes in the expression of NGF and its receptors. Both nandrolone and stanozolol increased NGF levels in the hippocampus and reduced NGF levels in the basal forebrain, reduced p75NTR expression in the hippocampus, and failed to affect TrkA expression in the basal forebrain. Finally, AASs treatment reduced the expression of choline acetyltransferase in the basal forebrain and impaired the behavioral performance in the Morris water maze. CONCLUSION: The evidence that supraphysiological doses of AASs cause neurotrophic unbalance and related behavioral disturbances, raises the concern that AASs abuse in humans may affect mechanisms that lie at the core of neuronal plasticity.

Data in animal models and surveys in humans have revealed psychiatric complications of long-term anabolic androgenic steroid abuse. However, the neurobiochemical mechanisms behind the observed behavioral changes are poorly understood. The aim of the present study was to investigate the effects of nandrolone decanoate on emotional behavior and neurochemical brain alterations in gonadally intact male rats. The behavioral reactivity to the elevated plus maze and the social interaction test was used to assess anxiety-related symptoms, and the sucrose preference test was used to evaluate anhedonia. Dopaminergic, serotonergic and noradrenergic transmissions were also evaluated in selected brain areas. The chronic administration of nandrolone, at 5 mg kg(-1) injected daily for 4 weeks, induced the loss of sweet taste preference, a sign of anhedonia and dysfunction of the reward pathway. The behavioral outcomes were accompanied by reductions in the dopamine, serotonin and noradrenaline contents in the nucleus accumbens. Alterations in the time spent in the open arms and in the social interaction test were not found, suggesting that nandrolone did not induce an anxiogenic profile. No differences were revealed between the experimental groups in the amygdala in terms of the neurotransmitters measured. Our data suggest that nandrolone-treated rats have a depressive, but not anxiogenic-like, profile, accompanied by brain region-dependent changes in dopaminergic, serotonergic and noradrenergic neurotransmission. As anabolic androgenic steroid dependence is plausibly the major form of worldwide substance dependence that remains largely unexplored, it should be highlighted that our data could contribute to a better understanding of the altered rewards induced by nandrolone treatment and to the development of appropriate treatments.

Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies.

Carvacrol is the major constituent of essential oils from aromatic plants. It showed antimicrobial, anticancer and antioxidant properties. Although it was approved for food use and included in the chemical flavorings list, no indication on its safety has been estimated. Since the use of plant extracts is relatively high among women, aim of this study was to evaluate carvacrol effects on female physiology and endocrine profiles by using female rats in proestrus and diestrus phases. Serotonin and metabolite tissue content in prefrontal cortex and nucleus accumbens, after carvacrol administration (0.15 and 0.45 g/kg p.o.), was measured. Drug effects in behavioral tests for alterations in motor activity, depression, anxiety-related behaviors and endocrine alterations were also investigated. While in proestrus carvacrol reduced serotonin and metabolite levels in both brain areas, no effects were observed in diestrus phase. Only in proestrus phase, carvacrol induced a depressive-like behavior in forced swimming test, without accompanying changes in ambulation. The improvement of performance in FST after subchronic treatment with fluoxetine (20 mg/kg) suggested a specific involvement of serotonergic system. No differences were found across the groups with regard to self-grooming behavior. Moreover, in proestrus phase, carvacrol reduced only estradiol levels without binding hypothalamic estradiol receptors. Our study showed an estrous-stage specific effect of carvacrol on depressive behaviors and endocrine parameters, involving serotonergic system. Given the wide carvacrol use not only as feed additive, but also as cosmetic essence and herbal remedy, our results suggest that an accurate investigation on the effects of its chronic exposure is warranted. (C) 2011 Elsevier Inc. All rights reserved.

It has been well documented that β-amyloid (Aβ) peptide accumulation and aggregation in the brain plays a crucial role in the pathophysiology of Alzheimer's disease (AD). However, a new orientation of the amyloid cascade hypothesis has evidenced that soluble forms of the peptide (sAβ) are involved in Aβ-induced cognitive impairment and cause rapid disruption of the synaptic mechanisms underlying memory. The primary aim of this study was to elucidate the effects of sAβ, acutely injected intracerebrally (i.c.v., 4 μM), on the short term and long term memory of young adult male rats, by using the novel object recognition task. Glutamatergic receptors have been proposed as mediating the effect of Aβ on synaptic plasticity and memory. Thus, we also investigated the effects of sAβ on prefrontal cortex (PFC) glutamate release and the specific contribution of N-methyl-D-aspartate (NMDA) receptor modulation to the effects of sAβ administration on the cognitive parameters evaluated. We found that a single i.c.v. injection of sAβ 2 h before testing did not alter the ability of rats to differentiate between a familiar and a novel object, in a short term memory test, while it was able to negatively affect consolidation/retrieval of long term memory. Moreover, a significant increase of glutamate levels was found in PFC of rats treated with the peptide 2 h earlier. Interestingly, memory deficit induced by sAβ was reversed by a NMDA-receptor antagonist, memantine (5 mg/kg i.p), administered immediately after the familiarization trial (T1). On the contrary, memantine administered 30 min before T1 trial, was not able to rescue long term memory impairment. Taken together, our results suggest that an acute i.c.v. injection of sAβ peptide interferes with the consolidation/retrieval of long term memory. Moreover, such sAβ-induced effect indicates the involvement of glutamatergic system, proposing that NMDA receptor inhibition might prevent or lead to the recovery of early cognitive impairment

In the South of Italy the use of herbal remedies to alleviate pregnancy-related symptoms is very common. To investigate the proportion, prevalence of use, attitude and knowledge base in a sample of Italian pregnant women in the South of Italy. To explore the possible influence and risks of herbal consumption on pregnancy and neonatal outcomes. A retrospective observational study was conducted during the study period November 2010-September 2013. Six hundred and thirty expectant mothers were interviewed within three days after childbirth in a public Hospital in the South of Italy. Due to a lack of data, a total of six hundred interviews were considered. Four hundred and eighty six women (81%) reported to have constantly used at least one herbal product throughout the pregnancy period. The study enrolled mostly women between 31 and 40 years of age, with a middle-high level of education, married and employed. The most commonly used herbal products, taken by oral route and for the entire period of pregnancy, were chamomile, fennel, propolis, cranberry, lemon balm, ginger, valerian and mallow. The most relevant source of information for the majority of participants was the doctor (95%), and most of the women (72%) informed their doctors about their use of herbal remedies. The regular chamomile consumption resulted in a higher risk of pre-term delivery, lower birth weight and lower length of the newborn. Also a regular use of fennel resulted in a shorter gestational age. Finally, ginger intake resulted in a shorter gestational age and in a smaller circumference of the newborn's skull.

Aims: Psychosocial stress alters the HPA-axis. Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress-response and in the pathogenesis of neurologic and psychiatric diseases. NOX enzymes are a major source of ROS in the CNS. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine alterations in a rat model of chronic psychosocial stress, the social isolation. Results: Significant elevations in the hypothalamic levels of CRF and plasmatic ACTH were observed from four weeks of social isolation. Increased levels of peripheral markers of the HPA-axis (plasmatic and salivary corticosterone) were observed at later time point of social isolation (seven weeks). Alteration in exploratory activity of isolated rats followed the same time course. Increased expression of markers of oxidative stress (8OhdG and nitrotyrosine) and NOX2 mRNA was early detectable in the hypothalamus of isolated rats (after two weeks), but later (after seven weeks) in the adrenal gland. A three-weeks-treatment with the antioxidant/NOX inhibitor apocynin stopped the progression of isolation-induced alterations of the HPA-axis. Rats with a loss of function mutation in the NOX2 subunit p47phox were totally protected from alterations of the neuroendocrine profile, behavior and increased NOX2 mRNA expression induced by social isolation. Innovation: We demonstrate that psychosocial stress induces early elevation of NOX2-derived oxidative stress in the hypothalamus and consequent alterations of the HPA-axis, leading ultimately to altered behavior. Conclusion: Pharmacological targeting of NOX2 might be of crucial importance for treatment of psychosocial stress-induced psychosis.

In isolated guinea-pig ileum (GPI), the κ-opioid acute withdrawal response is under the control of several neuronal signaling systems, including the μ-opioid, the A(1)-adenosine and the CB(1) receptors, which are involved in the inhibitory control of the κ-withdrawal response. After κ-opioid system stimulation, indirect activation of μ-opioid, A(1)-adenosine and CB(1) systems is prevented by the peptide cholecystokinin-8 (CCk-8). In the present study, we have investigated whether the NOP system is also involved in the regulation of the acute κ-withdrawal response. Interestingly, we found that in GPI preparation, the NOP system is not indirectly activated by the κ-opioid receptor stimulation, but instead this system is able by itself to directly regulate the acute κ-withdrawal response. Specifically, our results clearly highlight first the existence of an endogenous tone of the NOP system in GPI, and second that it behaves as a functional anti-opioid system. We also found that, the NOP receptor system is involved in the regulation of the CCk-8-induced contracture intensity, only when in the presence of the κ-opioid receptor stimulation. This effect seems to be regulated by an activation threshold mechanism. In conclusion, the NOP system could act as neuromodulatory system, whose action is strictly related to the modulation of both excitatory and inhibitory neurotransmitters released in GPI enteric nervous system.