Hypothalamic supraoptic but not paraventricular nucleus is involved in cardiovascular responses to carbachol microinjected into the bed nucleus of stria terminalis of unanesthetized rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chronic fluoxetine treatment alters cardiovascular functions in unanesthetized rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ionotropic Glutamate Receptors in Hypothalamic Paraventricular and Supraoptic Nuclei Mediate Vasopressin and Oxytocin Release in Unanesthetized Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The orexin receptor 1 in the locus coeruleus modulates the hypercapnic ventilatory response in unanesthetized rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chemoreflex and baroreflex alterations in Parkinsonism induced by 6-OHDA in unanesthetized rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cardiovascular effects of the microinjection of L-proline into the third ventricle or the paraventricular nucleus of the hypothalamus in unanesthetized rats

We investigated the cardiovascular effects of the microinjection of L-proline (L-Pro) into the third ventricle (3V) and its peripheral mechanisms. Different doses of L-Pro into the 3V caused dose-related pressor and bradycardiac responses. The pressor response to L-Pro injected into the 3V was potentiated by intravenous pretreatment with the ganglion blocker pentolinium (5 mg/kg), thus excluding any significant involvement of the sympathetic nervous system. Because the response to the microinjection of L-Pro into the 3V was blocked by intravenous pretreatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP (50 mu g/kg), it is suggested that these cardiovascular responses are mediated by a vasopressin release. The pressor response to the microinjection of L-Pro into the 3V was found to be mediated by circulating vasopressin, so, given that the paraventricular nucleus of the hypothalamus (PVN) is readily accessible from the 3V, we investigated whether the PVN could be a site of action for the L-Pro microinjected in the 3V. The microinjection of L-Pro (0.033 mu moles/0.1 mu l) into the PVN caused cardiovascular responses similar to those of injection of the 3V and were also shown to be mediated by vasopressin release. In conclusion, these results show that the microinjection of L-Pro into the 3V causes pressor and bradycardiac responses that could involve stimulation of the magnocellular cells of the PVN and release of vasopressin into the systemic circulation. Also, because the microinjection of L-Pro into the PVN caused a pressor response, this is the first evidence of cardiovascular effects caused by its injection in a supramedullary structure. (c) 2012 Wiley Periodicals, Inc.

Cardiovascular responses to glutamate microinjection in the dorsomedial periaqueductal gray of unanesthetized rats

The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Glutamate (L-Glu) is an abundant excitatory amino acid in the central nervous system (CNS) and is present in the rat PAG. Moreover, data in the literature indicate its involvement in central blood pressure control. Here we report on the cardiovascular effects caused by microinjection of L-Glu into the dorsomedial PAG (dmPAG) of rats and the glutamatergic receptors as well as the peripheral mechanism involved in their mediation. The microinjection of L-Glu into the dmPAG of unanesthetized rats evoked dose-related pressor and bradycardiac responses. The cardiovascular response was significantly reduced by pretreatment of the dmPAG with a glutamatergic M-methyl-D-aspartate (NMDA) receptor antagonist (LY235959) and was not affected by pretreatment with a non-NMDA receptor antagonist (NBQX), suggesting a mediation of that response by the activation of NMDA receptors. Furthermore, the pressor response was blocked by pretreatment with the ganglion blocker pentolinium (5 mg/kg, intravenously), suggesting an involvement of the sympathetic nervous system in this response. Our results indicate that the microinjection of L-Glu into the dmPAG causes sympathetic-mediated pressor responses in unanesthetized rats, which are mediated by glutamatergic NMDA receptors in the dmPAG. (c) 2012 Wiley Periodicals, Inc.

Ionotropic Glutamate Receptors in Hypothalamic Paraventricular and Supraoptic Nuclei Mediate Vasopressin and Oxytocin Release in Unanesthetized Rats

We report changes in plasma arginine vasopressin (AVP) and oxytocin (OT) concentrations evoked by the microinjection of L-glutamate (L-glu) into the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus(PVN) of unanesthetized rats, as well as which local mechanisms are involved in their mediation. L-Glu microinjection (10 nmol/100 nl) into the SON increased the circulating levels of both AVP and OT. The AVP increases were blocked by local pretreatment with the selective non-N-methyl-D-aspartate (NMDA) receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) (2 nmol/100 nl), but it was not affected by pretreatment with the NMDA-receptor antagonist LY235959 (2 nmol/100 nl). The OT response to L-glu microinjection into the SON was blocked by local pretreatment with either NBQX or LY235959. Furthermore, the administration of either the non-NMDA receptor agonist (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) (5 nmol/100 nl) or NMDA receptor agonist NMDA (5 nmol/100 nl) into the SON had no effect on OT baseline plasma levels, but when both agonists were microinjected together these levels were increased. L-Glu microinjection into the PVN did not change circulating levels of either AVP or OT. However, after local pretreatment with LY235959, the L-glu microinjection increased plasma levels of the hormones. The L-glu microinjection into the PVN after the local treatment with NBQX did not affect the circulating AVP and OT levels. Therefore, results suggest the AVP release from the SON is mediated by activation of non-NMDA glutamate receptors, whereas the OT release from this nucleus is mediated by an interaction of NMDA and non-NMDA receptors. The present study also suggests an inhibitory role for NMDA receptors in the PVN on the release of AVP and OT. (Endocrinology 153: 2323-2331, 2012)

Purinergic transmission in the rostral but not caudal medullary raphe contributes to the hypercapnia-induced ventilatory response in unanesthetized rats

The medullary raphe (MR) is a putative central chemoreceptor site, contributing to hypercapnic respiratory responses elicited by changes in brain PCO2/pH. Purinergic mechanisms in the central nervous system appear to contribute to central chemosensitivity. To further explore the role of P2 receptors within the rostral and caudal MR in relation to respiratory control in room air and hypercapnic conditions, we performed microinjections of PPADS, a non-selective P2X antagonist, in conscious rats. Microinjections of PPADS into the rostral or caudal MR produced no changes in the respiratory frequency, tidal volume and ventilation in room air condition. The ventilatory response to hypercapnia was attenuated after microinjection of PPADS into the rostral but not in the caudal MR when compared to the control group (vehicle microinjection). These data suggest that P2X receptors in the rostral MR contribute to the ventilatory response to CO2, but do not participate in the tonic maintenance of ventilation under room air condition in conscious rats. (C) 2012 Elsevier B.V. All rights reserved.

Opioid mu-receptors in the rostral medullary raphe modulate hypoxia-induced hyperpnea in unanesthetized rats

Aim: It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As opioid mu-receptors have been found in the MR, we studied the putative role of opioid mu-receptors in the rostral MR (rMR) region on ventilation in normal and 7% hypoxic conditions. Methods: We measured pulmonary ventilation ((V) over dotE) and the body temperatures (Tb) of male Wistar rats before and after the selective opioid l-receptor antagonist CTAP ( d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2, cyclic, 0.1 mu g per 0.1 mu L) was microinjected into the rMR during normoxia or after 60 min of hypoxia. Results: The animals treated with intra-rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia ( 430 +/- 86 mL kg) 1 min) 1) compared with the control group ( 790 +/- 82 mL kg) 1 min) 1) ( P < 0.05). No differences in the Tb were observed between groups during hypoxia. Conclusion: These data suggest that opioids acting on l-receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.

Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats

Abuse of cocaine and androgenic-anabolic steroids has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous illicit use of these substances, potential toxic interactions between cocaine and androgenic-anabolic steroids in the cardiovascular system are unknown. In the present study, we investigated the effect of single or combined administration of testosterone and cocaine for 1 or 10 consecutive days on basal cardiovascular parameters, baroreflex activity, and hemodynamic responses to vasoactive agents in unanesthetized rats. Ten-day combined administration of testosterone and cocaine increased baseline arterial pressure. Changes in arterial pressure were associated with altered baroreflex activity and impairment of both hypotensive response to intravenous sodium nitroprusside and pressor effect of intravenous phenylephrine. Chronic single administration of either testosterone or cocaine did not affect baseline arterial pressure. However, testosterone-treated animals presented rest bradycardia, cardiac hypertrophy, alterations in baroreflex activity, and enhanced response to sodium nitroprusside. Repeated administration of cocaine affected baroreflex activity and impaired vascular responsiveness to both sodium nitroprusside and phenylephrine. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present results suggest a potential interaction between toxic effects of cocaine and testosterone on the cardiovascular activity. Changes in baseline arterial pressure after combined administration of these 2 drugs may result from alterations in baroreflex activity and impairment of vascular responsiveness to vasoactive agents.

Behavioral and Autonomic Responses to Acute Restraint Stress Are Segregated within the Lateral Septal Area of Rats

Background: The Lateral Septal Area (LSA) is involved with autonomic and behavior responses associated to stress. In rats, acute restraint (RS) is an unavoidable stress situation that causes autonomic (body temperature, mean arterial pressure (MAP) and heart rate (HR) increases) and behavioral (increased anxiety-like behavior) changes in rats. The LSA is one of several brain regions that have been involved in stress responses. The aim of the present study was to investigate if the neurotransmission blockade in the LSA would interfere in the autonomic and behavioral changes induced by RS. Methodology/Principal Findings: Male Wistar rats with bilateral cannulae aimed at the LSA, an intra-abdominal datalogger (for recording internal body temperature), and an implanted catheter into the femoral artery (for recording and cardiovascular parameters) were used. They received bilateral microinjections of the non-selective synapse blocker cobalt chloride (CoCl(2), 1 mM/ 100 nL) or vehicle 10 min before RS session. The tail temperature was measured by an infrared thermal imager during the session. Twenty-four h after the RS session the rats were tested in the elevated plus maze (EPM). Conclusions/Significance: Inhibition of LSA neurotransmission reduced the MAP and HR increases observed during RS. However, no changes were observed in the decrease in skin temperature and increase in internal body temperature observed during this period. Also, LSA inhibition did not change the anxiogenic effect induced by RS observed 24 h later in the EPM. The present results suggest that LSA neurotransmission is involved in the cardiovascular but not the temperature and behavioral changes induced by restraint stress.

Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats

Background: Subcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is being investigated as a treatment for major depression. We report on the effects of ventromedial prefrontal cortex (vmPFC) DBS in rats, focusing on possible mechanisms involved in an antidepressant-like response in the forced swim test (FST). Methods: The outcome of vmPFC stimulation alone or combined with different types of lesions, including serotonin (5-HT) or nore-pineprhine (NE) depletion, was characterized in the FST. We also explored the effects of DBS on novelty-suppressed feeding, learned helplessness, and sucrose consumption in animals predisposed to helplessness. Results: Stimulation at parameters approximating those used in clinical practice induced a significant antidepressant-like response in the FST. Ventromedial PFC lesions or local muscimol injections did not lead to a similar outcome. However, animals treated with vmPFC ibotenic acid lesions still responded to DBS, suggesting that the modulation of fiber near the electrodes could play a role in the antidepressant-like effects of stimulation. Also important was the integrity of the serotonergic system, as the effects of DBS in the FST were completely abolished in animals bearing 5-HT, but not NE, depleting lesions. In addition, vmPFC stimulation induced a sustained increase in hippocampal 5-HT levels. Preliminary work with other models showed that DBS was also able to influence specific aspects of depressive-like states in rodents, including anxiety and anhedonia, but not helplessness. Conclusions: Our study suggests that vmPFC DES in rats maybe useful to investigate mechanisms involved in the antidepressant effects of SCG DBS.