Few data are available on adolescent users because most behavioral studies on anabolic-androgenic steroids (AAS) abuse have been performed in adults. Studies evaluating the impact of long-term effects of AAS abuse on the prepubertal phase are even more uncommon. Accordingly, this study was developed to test the hypothesis that changes induced by the use of AAS during the adolescent phase may be noted in the adult phase even when the AAS treatment cycle is discontinued. Therefore, not only behavioral changes but also possible autonomic and electrolyte disorders were evaluated. For this purpose, we used male prepubertal, 26-day-old (P26) Wistar rats that were treated with vehicle (control, n=10) or testosterone propionate (TP; 5 mg/kg intramuscular (IM) injection, AAS, n=10) five times per week for 5 weeks, totaling 25 applications during the treatment. Aggression tests were performed at the end of the cycle (P54-56), whereas open-field tests (OFTs), elevated plus maze (EPM) behavioral tests and measurements of heart rate variability (HRV), fluid intake and pathology were conducted in the adult phase (P87-92). The AAS group showed greater aggressiveness in the pubertal phase and higher levels of horizontal and vertical exploration and anxiety-related behavior in the adult phase than the control group (P<0.05). HRV tests showed an increase in sympathetic autonomic modulation, and hydroelectrolytic assessment showed lower basal intake levels of hypertonic saline than the control group (P<0.05), without statistically significant changes in the basal intake of water. These data together suggest that the use of AAS during the prepubertal phase induces behavioral, autonomic and hydroelectrolytic changes that manifest in the adult phase even when treatment is discontinued in late adolescence in rats.
The association between caffeine consumption and various psychiatric manifestations has long been observed. The objective was to assess the behavioral profile in offspring of Swiss mice treated during pregnancy and lactation with caffeine. For this purpose, two groups (n = 6 each and BW ~ 35 g) of female mice were treated during pregnancy and lactation by: tap water and caffeine solution at a concentration of 0.3 mg/mL through oral route. The offspring obtained, by completing 70 days of life, was underwent a behavioral battery test. Statistical analysis was performed by student t test and the different significance adopted was p < 0.05. According to our results, it was not found any significant differences in tail suspension and forced swimming tests. In anxiety related responses however, the mice of caffeine group had greater number of fecal pellets (178 %, p = 0.001) in the open field test, higher number of attempts (51 %, p = 0.03) in light-dark box and decreased percentage of entries in open arms (41 %, p = 0.01) in elevated plus maze test. Moreover, in the marble burying test, there was a significant decrease in the number of buried marbles compared with controls (110 %, p = 0,002). In the meantime, in the von Frey test, it was observed an exacerbation of mechanical allodynia both in basal conditions and after the carrageenan administration (p < 0.001). Furthermore, caffeine treatment during pregnancy and lactation causes long-term behavioral changes in the mice offspring that manifest later in life.
IntroductionVasopressin (AVP) and oxytocin (OXT) are neuropeptides produced by magnocellular neurons (MCNs) of the hypothalamus and secreted through neurohypophysis to defend mammals against dehydration. It was recently demonstrated that MCNs also project to limbic structures, modulating several behavioral responses.Methods and ResultsWe found that 24 h of water deprivation (WD) or salt loading (SL) did not change exploration or anxiety-like behaviors in the elevated plus maze (EPM) test. However, rats deprived of water for 48 h showed reduced exploration of open field and the closed arms of EPM, indicating hypoactivity during night time. We evaluated mRNA expression of glutamate decarboxylase 1 (Gad1), vesicular glutamate transporter 2 (Slc17a6), AVP (Avpr1a) and OXT (Oxtr) receptors in the lateral habenula (LHb), basolateral (BLA) and central (CeA) amygdala after 48 h of WD or SL. WD, but not SL, increased Oxtr mRNA expression in the CeA. Bilateral pharmacological inhibition of OXTR function in the CeA with the OXTR antagonist L-371,257 was performed to evaluate its possible role in regulating the EPM exploration or water intake induced by WD. The blockade of OXTR in the CeA did not reverse the hypoactivity response in the EPM, nor did it change water intake induced in 48-h water-deprived rats.DiscussionWe found that WD modulates exploratory activity in rats, but this response is not mediated by oxytocin receptor signaling to the CeA, despite the upregulated Oxtr mRNA expression in that structure after WD for 48 h.
Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of neonatal treatment of d-fenfluramine (d-FEN), a serotonin (5-HT) releaser, on the behavioral expression of adult male Swiss mice. For this purpose, we divided pregnant female Swiss mice into two groups (n = 6 each and $35 g). Their offspring were treated with d-FEN (3 mg/kg, s.c.) from postnatal days (PND) 5 to 20. At PND 21, one male puppy of each litter was euthanized; the midbrain and the hippocampus were dissected for RNA analysis. At PND 70, the male offspring underwent a behavioral assessment in the open field, elevated plus-maze, light-dark box, tail suspension, and rotarod test. The programmed animals had a decrease in 5HT1a, serotonin transporter (SERT), and brain-derived neurotrophic factor (BDNF) expression in the mesencephalic raphe region. Alternatively, there was a reduction only in the tryptophan hydroxylase (TPH2) and BDNF expression in the hippocampus. In the light-dark box test, offspring of the treated group had higher latency to light and less time on the light side than the control. Also, it was observed less time of immobility in the tail suspension test. We also observed low motor skill learning in the rotarod test. These findings suggest that programming with d-FEN during the neonatal period alters a mesencephalic and hippocampal serotonergic system, promoting anxiety, antidepressant behavior, low coordination, and motor learning in adults.
We have shown that ovarariectomized (OVX) rats exhibited higher salt intake compared to estrogen‐replaced rats (OVX+E2) particularly in models of induction of sodium appetite dependent on angiotensin II and low sodium plasma levels. This result was ascribed to enhanced AT1 receptors activity. In male rats we reported that repeated 5‐HT1A agonist administration reduced sodium appetite response related to somatodendritic 5‐HT1A autoreceptor desensitization. Therefore, we investigate the effect of systemic acute and chronic 8‐OH‐DPAT administration on the sodium appetite in normally hydrated or sodium‐depleted Wistar rats (furosemide, 20mg/kg, sc, 24h before experiment) in OVX+oil and OVX estrogen replaced (OVX+E2, estradiol cypionate, 10μg/animal) rats. Acute 8‐OH‐DPAT (250μg/kg, ip, during 7 days) induced an increase of 0.3M NaCl intake. OVX+E2 rats were not responsive to 5‐HT1A agonist in basal condition. Chronic administration of 8‐OH‐DPAT reduced the saline intake compared to OVX+vehicle, control group (2.3±0.17ml/100g vs 4.2±0.2ml/100g, at 120 min after fluids presentation) in sodium‐depleted rats. E2 replacement strengthened the antinatriorexigenic response of OVX+8‐OH‐DPAT treated rats (1.7±0.1ml/100g vs 4.2ml/100g, at 120 min after fluids presentation). Results suggest that chronic administration of 5‐HT1A agonist associated with E2 replacement therapy differentially trigger mechanisms for neural signaling to sodium satiety, possibly through recruitment of serotonergic pathways in the dorsal raphe nucleus.Support: FAPERJ & CNPq
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