RESUMO
The aim of this study was to evaluate female rat sexual motivation in a model of diabetes mellitus type 1. Severe hyperglycemia was induced in ovariectomized Wistar rats by injecting streptozotocin [STZ, 100 mg/kg, i.p.]. Ten days later, females received estradiol benzoate (10 µg/rat, s.c.) plus progesterone (3 mg/rat, s.c.). A group of STZ-treated animals was administered with insulin (2-4 U) every 12 h for 10 days, which normalized glucose levels. In the partner preference (PP) and sexual incentive motivation (SIM) tests, control females spent more time close to a sexually experienced male (SE) than with a castrated male (CM). STZ-treated females stayed the same amount of time with both stimuli, that is, they lost their sexual preference. We also evaluated the sense of smell using two behavioral tests, one related to sexual odors (SO) and another one to food odors (FO). In the SO test, control females spent more time sniffing the sawdust coming from cages that contained SE males; hyperglycemic females remained the same amount of time sniffing the sawdust of both stimuli: SE and CM. In the FO test, no differences were found between control and STZ-treated groups. Insulin treatment reverted the changes observed in hyperglycemic females in the PP, SIM and SO tests. These data suggest that severe hyperglycemia decreases sexual motivation and that insulin recovers such diminution.
Assuntos
Diabetes Mellitus , Insulina , Animais , Feminino , Insulina/farmacologia , Masculino , Motivação , Ratos , Ratos Wistar , Comportamento Sexual Animal , EstreptozocinaRESUMO
BACKGROUND: Rutin is a bioflavonoid found in fruits, vegetables and plants used in traditional medicine to alleviate pain. However, rutin's scientific evidence for the modulation of pain and its mechanism of action is lacking. It is well known that the periaqueductal grey matter (PAG) contains opioidergic neural circuits involved in the modulation of descending nociception. The aim of this study was to investigate if antinociceptive activity of rutin is modulated by the PAG circuitry involving participation of opioid receptors. METHODS: The experimental design included groups of rats receiving rutin systemically (30-1000 mg/kg) or microinjected into the vlPAG (8-32 nmol/4 µL) alone or in the presence of an opioid antagonist, naltrexone (5 mg/kg, i.p. or 26 nmol/4 µL, respectively). Nociception was assessed using the formalin test and compared versus the reference drugs, tramadol and morphine. RESULTS: Systemic or intra-vlPAG administration of rutin significantly decreased both phases of the formalin test. Antinociceptive responses of the reference drugs were prevented by naltrexone, whereas the antinociceptive effect of rutin was inhibited by this antagonist mainly in the phase II of the formalin test. CONCLUSIONS: Our results provide evidence that rutin produces antinociceptive effects involving central modulation of the vlPAG descending circuit partly mediated by an opioidergic mechanism.
Assuntos
Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Nociceptividade/efeitos dos fármacos , Dor/tratamento farmacológico , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Rutina/uso terapêutico , Animais , Masculino , Microinjeções , Morfina/farmacologia , Morfina/uso terapêutico , Entorpecentes/farmacologia , Entorpecentes/uso terapêutico , Medição da Dor , Ratos , Ratos Wistar , Receptores Opioides/agonistas , Rutina/farmacologia , Tramadol/farmacologia , Tramadol/uso terapêuticoRESUMO
Animal studies and clinical investigations reveal that serotonin plays a central role in the control of the ejaculatory threshold. The chronic use of selective serotonin reuptake inhibitors (SSRIs) frequently results in sexual dysfunction, inviting to analyze the modulatory actions of serotonin on male sexual function in depth. Even though the main effect of serotonin on male sexual responses is inhibitory, this neuromodulator also mediates brief important stimulatory actions. Serotonin (5-HT) can activate two intracellular signaling pathways: a lower-threshold facilitatory pathway, and a higher-threshold inhibitory pathway, leading to biphasic effects. We propose that these divergent actions are related to the stimulation or inhibition of glutamatergic and GABAergic interneurons. Experimental evidence suggests that low 5-HT concentrations produce stimulatory actions on male ejaculatory aspects that might be mediated by the blockade of the GABAergic neurotransmission in the MPOA and spinal cord, which in turn releases a tonic inhibition that allows other neurotransmitters such as glutamate, noradrenaline, oxytocin and dopamine to initiate a sequence of molecular events resulting in the expression of ejaculation. Similar serotonin actions, mediated via interneurons, have been proposed for the regulation of other processes and occur in many central nervous system areas, indicating that it is not an isolated phenomenon.
Assuntos
Encéfalo/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Serotonina/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Ácido Glutâmico/metabolismo , Masculino , Ratos , Serotonina/metabolismo , Serotoninérgicos/farmacologia , Comportamento Sexual Animal/fisiologia , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologiaRESUMO
Sex differences exist in the depressive disorder prevalence and response to treatment. Several studies suggest that females respond better than males to the action of selective serotonin reuptake inhibitors (SSRIs), suggesting that gonadal hormones modulate mood and the response to these drugs. Sexual steroid hormones exert organizational actions (perennial and on early development) and activational effects (transient and on differentiated tissues). The aim of this study was to analyze sex differences in the forced swim test (FST) in animals without treatment and after fluoxetine (FLX, 0, 2.5, 5.0 and 10.0mg/kg). Initially, we compared male and female adult rats under control conditions or after altering their sexual differentiation process (at day 5 postnatally, PN, 60µg of testosterone propionate to females and male castration to induce or preclude masculinization, respectively). To further analyze if the sex differences depend on organizational or activational steroid hormone action we tested the same animals before and after adult gonadectomy. To prevent variations depending upon the estrous cycle, control and masculinized females were tested in estrus. Control females showed lower immobility and required lower doses of FLX (5mg/kg), to show an antidepressant-like effect, than males (10mg/kg), even after adult gonadectomy. In control males adult orchidectomy prevented FLX's action. Neonatally masculinized females exhibited analogous levels of immobility than control ones; before ovariectomy they responded to FLX similar to controls, but after the surgery they did not respond to fluoxetine. Neonatally orchidectomized males exhibited similar immobility values and response to FLX than control females. The findings suggest that the sex difference in despair depends on the hormones organizational effects and, in males, the response to FLX relies on organizational and activational actions.
Assuntos
Antidepressivos de Segunda Geração/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Depressão/tratamento farmacológico , Fluoxetina/farmacologia , Hormônios Esteroides Gonadais/metabolismo , Caracteres Sexuais , Fatores Etários , Androgênios/farmacologia , Animais , Antidepressivos de Segunda Geração/administração & dosagem , Depressão/fisiopatologia , Estro , Feminino , Fluoxetina/administração & dosagem , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Testes Neuropsicológicos , Orquiectomia , Ovariectomia , Distribuição Aleatória , Ratos , Ratos Wistar , Natação , Testosterona/farmacologiaRESUMO
INTRODUCTION: A possible hormonal influence in language development has been suggested in the recent years. The 2D:4D finger ratio is an indirect measure for prenatal androgen exposure. It is negatively related to prenatal testosterone and positively related to prenatal estrogen, resulting in a lower ratio for men and a larger ratio for women. It can be explored in children as young as 2 years old. AIM: To study if an association exists between the 2D:4D finger ratio and language development (vocabulary) and/or language problems. SUBJECTS AND METHODS: The lengths of the second digit (index finger) (2D) and the fourth digit (ring finger) (4D) were measured in 97 preschoolers and the Language Development Survey was administered to the parents. RESULTS: A weak negative correlation between language development (vocabulary) and right 2D:4D ratio was found in both sexes for children aged 4 or less years, significant only in boys. A strong negative correlation between language articulation problems and right 2D:4D ratio in both sexes for children aged 3 or less years, and a lower negative correlation between articulation problems and right 2D:4D ratio were found for boys aged 4 or less years. CONCLUSION: Findings suggest an important role for testosterone in language development (vocabulary) and a possible influence on articulation problems, probably through higher testosterone levels.
Assuntos
Dedos/anatomia & histologia , Desenvolvimento da Linguagem , Pré-Escolar , Estrogênios/metabolismo , Feminino , Dedos/embriologia , Humanos , Lactente , Masculino , Testosterona/metabolismoRESUMO
RATIONALE: Antidepressants (ADs) are slow to produce their therapeutic effect. This long latency promotes the development of new strategies to short their onset of action. Previous reports indicated that 17beta-estradiol (E(2)) promotes the antidepressant-like activity of fluoxetine (FLX) and desipramine (DMI) in the forced swimming test (FST). OBJECTIVE: The aim of the present work was to analyze if E(2) reduces the antidepressant-like onset of action of venlafaxine (VLX), FLX, and DMI. MATERIALS AND METHODS: Independent groups of ovariectomized female Wistar rats were tested in the FST and in the open field after chronic (1 to 14 days) treatment with VLX (20 mg/kg/day), FLX (1.25 mg/kg/day), or DMI (1.25 mg/kg/day) alone or in combination with a single injection of E(2) (2.5 microg/rat sc, 8 h before FST). RESULTS: VLX, FLX, or DMI by themselves at these doses did not induce changes in the FST at short intervals after their injection (from 1 to 7 days). The addition of E(2) promoted the antidepressant-like effect of VLX and DMI as early as day 1. Such action was also evident after 3, for FLX, and 14 days for both FLX and DMI, but not for VLX. The behavioral actions of these ADs combined with E(2) were not accompanied by increases in general activity in the open-field test. CONCLUSION: E(2) clearly reduced the latency to the onset of action for these ADs in the FST. These results represent an interesting therapeutic strategy for the treatment of depression in perimenopausal women.
Assuntos
Antidepressivos de Segunda Geração/farmacologia , Comportamento Animal/efeitos dos fármacos , Estradiol/farmacologia , Tempo de Reação/efeitos dos fármacos , Natação/psicologia , Inibidores da Captação Adrenérgica/farmacologia , Animais , Cicloexanóis/farmacologia , Desipramina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Estrogênios/farmacologia , Feminino , Fluoxetina/farmacologia , Injeções Subcutâneas , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Ovariectomia , Ratos , Ratos Wistar , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Natação/fisiologia , Cloridrato de VenlafaxinaRESUMO
The objective of this study was to establish the effect of aging on the development of anhedonia, a core feature of depression. Young and old male Wistar rats (of around 3-5 and 12-15 months, respectively) were exposed to a chronic variable stress (CVS) schedule for 3 weeks. CVS produced anhedonia, indicated by a reduction in the intake of a sucrose solution (1%), in 8 out of 23 (35%) young rats and in 19 out of 26 (73%) old rats, implying that old animals are more susceptible to stress and develop anhedonia more readily than young animals. Young and old anhedonic rats showed a similar temporal course in the reduction of sucrose consumption, reaching the anhedonic state after 2 weeks of CVS exposure. Compared with young animals, old rats had lower basal serum testosterone and estradiol levels. The systemic levels of corticosterone did not vary between both age groups. No significant pathological condition was detected in old animals. It is suggested that the higher susceptibility to develop anhedonia in male rats could be associated to neuroendocrine changes consequent to aging.
Assuntos
Envelhecimento , Depressão/etiologia , Suscetibilidade a Doenças , Estresse Psicológico/complicações , Análise de Variância , Animais , Doença Crônica , Condicionamento Operante/fisiologia , Corticosterona/sangue , Depressão/sangue , Ingestão de Líquidos/fisiologia , Ingestão de Alimentos/fisiologia , Estradiol/sangue , Preferências Alimentares , Masculino , Ratos , Ratos Wistar , Testosterona/sangueRESUMO
Lactating dams and maternal virgin females are less fearful in behavioral tests compared with non-maternal animals, suggesting that maternal condition per se reduces the negative value of threatening stimuli. In addition, lactating females exhibit a diminished hypothalamic-pituitary-adrenal response to potential environmental threats. Can the maternal condition, independently of the endocrine profile of lactation, promote a reduction in the behavioral as well as in the endocrine response to an emotional stressor? To answer this question, anxiety-related and fear behaviors as well as the levels of corticosterone were evaluated in response to a bright-lit open field-loud noise model in maternal and non-maternal non-ovariectomized virgin females and lactating dams in the presence of the pups. Maternal animals, both lactating and virgin, presented an increased exploration of the bright-lit open field and a significant reduction of fear behaviors, indicated by the decreased flight and immobility responses to the subsequent activation of a loud noise, in comparison to non-maternal virgins. Interestingly, maternal virgin females, as non-maternal rats, showed high corticosterone plasma levels, in contrast to the lower endocrine response exhibited by lactating dams when confronted to this threat. Present results suggest that maternal condition allows females to take risks when caring for their young, a behavioral strategy that is independent of the reduced hypothalamic-pituitary-adrenal axis response characteristic of lactation. This evidence points towards a clear dissociation in the mechanisms regulating behavioral and endocrine responses to emotional stressors during motherhood.
Assuntos
Adaptação Psicológica , Corticosterona/sangue , Ciclo Estral/fisiologia , Medo/fisiologia , Comportamento Materno/fisiologia , Estresse Psicológico/sangue , Estimulação Acústica , Adaptação Fisiológica , Análise de Variância , Animais , Comportamento Exploratório/fisiologia , Medo/psicologia , Feminino , Sistema Hipotálamo-Hipofisário/fisiologia , Inibição Psicológica , Lactação/fisiologia , Comportamento Materno/psicologia , Paridade/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Gravidez , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
The long term inhibition of masculine sexual behavior after repeated ejaculations is known as sexual satiety. To investigate the brain areas that may regulate sexual satiety, c-Fos expression was studied in different groups of sexually experienced male rats: controls not allowed to copulate, males allowed two or four ejaculations and animals allowed to reach sexual satiety. Interestingly, males that ejaculated two or four times had similar c-Fos densities in all the evaluated brain regions, except for the suprachiasmatic nucleus. Similarly, sexually satiated males had analogous c-Fos densities in all the evaluated brain areas independently of the number of ejaculations required to reach satiety. Sexual activity (evidenced in males that ejaculated two or four times) increased c-Fos levels in the anteromedial bed nucleus of the stria terminalis, claustrum, entorhinal cortex, medial preoptic area, nucleus accumbens core, suprachiasmatic nucleus and supraoptic nucleus; however, sexual satiety did not modify c-Fos expression in these regions. Sexually satiated males had increased c-Fos densities in the ventrolateral septum and the anterodorsal and posteroventral medial amygdala, compared with animals allowed to copulate but that did not reach sexual satiety, and decreased c-Fos density in the piriform cortex. These results suggest that the network that underlies sexual satiety is different from that which regulates copulation.
Assuntos
Mapeamento Encefálico , Sistema Límbico/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Saciação/fisiologia , Comportamento Sexual Animal/fisiologia , Tonsila do Cerebelo/metabolismo , Animais , Imuno-Histoquímica , Masculino , Condutos Olfatórios/metabolismo , Giro Para-Hipocampal/metabolismo , Prosencéfalo/metabolismo , Ratos , Ratos Wistar , Septo do Cérebro/metabolismoRESUMO
RATIONALE: The effect of anxiety on nociception has been evaluated but not that of nociception on anxiety. OBJECTIVE: The study was conducted to analyse the influence of nociception on basal levels of anxiety-like behaviour and on the action of anxiolytic drugs. METHODS: Nociception was induced by an intra-articular injection of uric acid at 3.75 or 7.5%. Experimental anxiety was determined in the rat burying behaviour and the elevated plus maze tests. To separate specific anxiety-related drug actions, a spontaneous ambulatory test was included. The anxiolytics, buspirone (2.5 and 5.0 mg/kg, i.p.) and diazepam (0.5, 1.0 and 2.0 mg/kg, i.p.), were used. RESULTS: In the nociception test, the pain-induced functional impairment rat model, uric acid at 3.75 and 7.5% had an effect of around 35 and 75%, respectively. Uric acid (UA) at the lower dose (3.75%) lacked an effect on burying behaviour but significantly increased the time spent and number of entries to the open arms; the higher UA dose (7.5%) produced a significant increase in the time spent and number of entries to the open arms and a statistically significant reduction in cumulative burying. Diazepam and buspirone produced a clear dose-dependent reduction in cumulative burying. In the plus maze, diazepam also induced an increase in the time spent and number of entries to the open arms. In the burying behaviour test, rats with a mild level of nociception (uric acid at 7.5%) were insensitive to the anxiolytic-like effect of these anxiolytic drugs. In the plus maze test, the anxiolytic-like effect of diazepam (1.0 mg/kg) was blocked under both levels of nociception. CONCLUSIONS: These data demonstrate that nociception modifies the response to anxiolytic drugs. The role of factors with anxiogenic properties produced during inflammation, which may modify diazepam and buspirone effects, is discussed.