RESUMEN
AIMS: Acute restraint stress (RS) has been reported to cause neuronal activation in the supraoptic nucleus of the hypothalamus (SON). The aim of the study was to evaluate the role of SON on autonomic (mean arterial pressure [MAP], heart rate [HR], and tail temperature), neuroendocrine (corticosterone, oxytocin, and vasopressin plasma levels), and behavioral responses to RS. METHODS: Guide cannulas were implanted bilaterally in the SON of male Wistar rats for microinjection of the unspecific synaptic blocker cobalt chloride (CoCl2, 1 mM) or vehicle (artificial cerebrospinal fluid, 100 nL). A catheter was introduced into the femoral artery for MAP and HR recording. Rats were subjected to RS, and it was studied the effect of microinjection of CoCl2 or vehicle into the SON on pressor and tachycardic responses, drop in tail temperature, plasma oxytocin, vasopressin, and corticosterone levels, and anxiogenic-like effect induced by RS. RESULTS: SON pretreatment with CoCl2 reduced the RS-induced MAP and HR increase, without affecting the RS-evoked tail temperature decrease. Microinjection of CoCl2 into areas surrounding the SON did not affect RS-induced increase in MAP and HR, reinforcing the idea that SON influences RS-evoked cardiovascular responses. Also, SON pretreatment with CoCl2 reduced RS-induced increase in corticosterone and oxytocin, without affecting vasopressin plasma levels, suggesting its involvement in RS-induced neuroendocrine responses. Finally, the CoCl2 microinjection into SON inhibited the RS-caused delayed anxiogenic-like effect. CONCLUSION: The results indicate that SON is an important component of the neural pathway that controls autonomic, neuroendocrine, and behavioral responses induced by RS.
Asunto(s)
Sistema Nervioso Autónomo , Conducta Animal/fisiología , Sistemas Neurosecretores , Restricción Física/fisiología , Estrés Psicológico , Núcleo Supraóptico/fisiología , Animales , Sistema Nervioso Autónomo/metabolismo , Sistema Nervioso Autónomo/fisiopatología , Modelos Animales de Enfermedad , Masculino , Sistemas Neurosecretores/metabolismo , Sistemas Neurosecretores/fisiopatología , Ratas , Ratas Wistar , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatologíaRESUMEN
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(CH(2) )(5) (Me)AVP (50µg/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 µmoles/0.1 µl) 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.
Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Prolina/administración & dosificación , Tercer Ventrículo/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Microinyecciones , Ratas , Ratas WistarRESUMEN
Medial amygdaloid nucleus (MeA) neurotransmission has an inhibitory influence on cardiovascular responses in rats submitted to restraint, which are characterized by both elevated blood pressure (BP) and intense heart rate (HR) increase. In the present study, we investigated the involvement of MeA adrenoceptors in the modulation of cardiovascular responses that are observed during an acute restraint. Male Wistar rats received bilateral microinjections of the selective α1-adrenoceptor antagonist WB4101 (10, 15, and 20 nmol/100 nL) or the selective α2-adrenoceptor antagonist RX821002 (10, 15, and 20 nmol/nL) into the MeA, before the exposure to acute restraint. The injection of WB4101 reduced the restraint-evoked tachycardia. In contrast, the injection of RX821002 increased the tachycardia. Both drugs had no influence on BP increases observed during the acute restraint. Our findings indicate that α1 and α2-adrenoceptors in the MeA play different roles in the modulation of the HR increase evoked by restraint stress in rats. Results suggest that α1-adrenoceptors and α2-adrenoceptors mediate the MeA-related facilitatory and inhibitory influences on restraint-related HR responses, respectively.
Asunto(s)
Amígdala del Cerebelo/fisiología , Receptores Adrenérgicos alfa 1/fisiología , Receptores Adrenérgicos alfa 2/fisiología , Estrés Psicológico/fisiopatología , Antagonistas Adrenérgicos alfa/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Dioxanos/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Idazoxan/análogos & derivados , Idazoxan/farmacología , Masculino , Ratas , Ratas Wistar , Restricción Física/fisiologíaRESUMEN
The medial amygdaloid nucleus (MeA) is involved in the modulation of physiological and behavioral processes, as well as regulation of the autonomic nervous system. Moreover, MeA electrical stimulation evokes cardiovascular responses. Thus, as noradrenergic receptors are present in this structure, the present study tested the effects of local noradrenaline (NA) microinjection into the MeA on cardiovascular responses in conscious rats. Moreover, we describe the types of adrenoceptor involved and the peripheral mechanisms involved in the cardiovascular responses. Increasing doses of NA (3, 9, 27 or 45 nmol/100 nL) microinjected into the MeA of conscious rats caused dose-related pressor and bradycardic responses. The NA cardiovascular effects were abolished by local pretreatment of the MeA with 10 nmol/100 nL of the specific α2-receptor antagonist RX821002, but were not affected by local pretreatment with 10 nmol/100 nL of the specific α1-receptor antagonist WB4101. The magnitude of pressor response evoked by NA microinjected into the MeA was potentiated by intravenous pretreatment with the ganglion blocker pentolinium (5 mg/kg), and blocked by intravenous pretreatment with the selective V1-vasopressin antagonist dTyr(CH2)5 (Me)AVP (50 µg/kg). In conclusion, our results show that microinjection of NA into the MeA of conscious rats activates local α2-adrenoceptors, evoking pressor and bradycardic responses, which are mediated by vasopressin release.
Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Norepinefrina/farmacología , Receptores Adrenérgicos alfa 2/metabolismo , Vasopresinas/metabolismo , Antagonistas Adrenérgicos alfa/farmacología , Amígdala del Cerebelo/anatomía & histología , Animales , Dioxanos/farmacología , Masculino , Microinyecciones , Antagonistas Nicotínicos/farmacología , Tartrato de Pentolinio/farmacología , Ratas , Ratas Wistar , Vasoconstrictores/metabolismoRESUMEN
The ventral medial prefrontal cortex (vMPFC) has direct connections to subcortical, diencephalic and brainstem structures that have been closely related to depression. However, studies aimed at investigating the role of the vMPFC in the neurobiology of depression have produced contradictory results. Moreover, the precise involvement of vMPFC anatomic subdivisions, the prelimbic (PL) and the infralimbic (IL) cortices, in regulating depressive-like behavior have been poorly investigated. The forced swimming test (FST) is a widely employed animal model aimed at detecting antidepressant-like effects. Therefore, to further investigate a possible involvement of the vMFPC in depressive-like behavior, rats bilaterally implanted with cannulae aimed at the PL or IL prefrontal cortices were submitted to 15 min of forced swimming (pre-test) followed, 24h later, by a 5-min swimming session (test), where immobility time was registered. Synaptic transmission in these regions was temporarily inhibited using local microinjection of cobalt chloride at different periods of the experimental procedure (before or after the pre-test or before the test). PL inactivation decreased immobility time independently of the time of the injection. In the IL, inactivation induced a significant antidepressant-like effect when performed immediately before the pre-test or before the test, but not after the pre-test. These results suggest that activation of the vMPFC is important for the behavioral changes observed in rats submitted to the FST. They further indicate that, although both the PL and IL cortices are involved in these effects, they may play different roles.
Asunto(s)
Antidepresivos/farmacología , Depresión/fisiopatología , Corteza Prefrontal/fisiología , Transmisión Sináptica/efectos de los fármacos , Animales , Cobalto/administración & dosificación , Cobalto/farmacología , Modelos Animales de Enfermedad , Masculino , Microinyecciones , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Corteza Prefrontal/efectos de los fármacos , Ratas , Ratas Wistar , Natación/fisiologíaRESUMEN
The medial prefrontal cortex (MPFC) is involved in cardiovascular control. MPFC electrical stimulation has been reported to cause depressor and bradycardic responses in anesthetized rats. Although the pathway involved is yet unknown, there is evidence indicating the existence of a relay in the lateral hypothalamus (LH). The medial forebrain bundle (MFB) that courses in the lateral portion of the LH carries the vast majority of telencephalic afferent as well efferent projections, including those from the MPFC. To evaluate if the hypotensive pathway originating in the MPFC courses the MFB, we studied the effect of coronal or sagittal knife cuts through the LH and other brain areas on the cardiovascular responses to MPFC electrical stimulation. Knife cuts were performed using blades 1 to 6 mm wide. Results indicate that the neural pathway descending from the MFB decussates early in the vicinity of MPFC, crossing the midline within the corpus callosum and yielding two descending pathways that travel rostro-caudally in the lateral portion of the LH, within the MFB. The decussation was confirmed by histological analysis of brain sections processed after the injection of biotinilated dextran amine in the site of the stimulation in the MPFC. Because knife cuts through the LH ipsilateral had minimal effects on the cardiovascular responses and knife cuts performed contralateral to the stimulated MPFC had no effect on the response to MPFC stimulation, data indicate that the contralateral limb of the pathway may be only activated as an alternative pathway when the ipsilateral pathway is blocked.
Asunto(s)
Vías Autónomas/fisiología , Fenómenos Fisiológicos Cardiovasculares , Diencéfalo/fisiología , Haz Prosencefálico Medial/fisiología , Corteza Prefrontal/fisiología , Animales , Vías Autónomas/anatomía & histología , Biotina/análogos & derivados , Mapeo Encefálico , Desnervación , Dextranos , Diencéfalo/anatomía & histología , Vías Eferentes/anatomía & histología , Vías Eferentes/fisiología , Estimulación Eléctrica , Lateralidad Funcional/fisiología , Área Hipotalámica Lateral/anatomía & histología , Área Hipotalámica Lateral/fisiología , Masculino , Haz Prosencefálico Medial/anatomía & histología , Corteza Prefrontal/anatomía & histología , Ratas , Ratas Wistar , Coloración y EtiquetadoRESUMEN
The lateral septal area (LSA) is a part of the limbic system and is involved in cardiovascular modulation. We previously reported that microinjection of noradrenaline (NA) into the LSA of unanesthetized rats caused pressor responses that are mediated by acute vasopressin release. Magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) of the hypothalamus synthesize vasopressin. In the present work, we studied which of these nuclei is involved in the pressor pathway activated by unilateral NA injection into the LSA as well as the local neurotransmitter involved. Chemical ablation of the SON by unilateral injection of the nonspecific synapses blocker cobalt chloride (1 mM/100 nl) did not affect the pressor response evoked by NA (21 nmol/200 nl) microinjection into the LSA. However, the response to NA was blocked when cobalt chloride (1 mM/100 nl) was microinjected into the PVN, indicating that this hypothalamic nucleus is responsible for the mediation of the pressor response. There is evidence in the literature pointing to glutamate as a putative neurotransmitter activating magnocellular neurons. Pretreatment of the PVN with the selective non-N-methyl-D-asparate (NMDA) antagonist NBQX (2 nmol/100 nl) blocked the pressor response to NA microinjected into the LSA, whereas pretreatment with the selective NMDA antagonist LY235959 (2 nmol/100 nl) did not affect the response to NA. Our results implicate the PVN as the final structure in the pressor pathway activated by the microinjection of NA into the LSA. They also indicate that local glutamatergic synapses and non-NMDA glutamatergic receptors mediate the response in the PVN.
Asunto(s)
Fenómenos Fisiológicos Cardiovasculares , Sistema Límbico/efectos de los fármacos , Norepinefrina/administración & dosificación , Núcleo Hipotalámico Paraventricular/metabolismo , Receptores de Glutamato/metabolismo , Animales , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Glutámico/metabolismo , Inyecciones Intraventriculares , Masculino , Microinyecciones , N-Metilaspartato/metabolismo , Ratas , Ratas Wistar , Vasopresinas/metabolismoRESUMEN
The septal lateral area (LSA) is a limbic structure that is involved with autonomic and behavioral responses. In the present study we report the effect of acute and reversible LSA synaptic inhibition on the parasympathetic and the sympathetic components of baroreflex in unanesthetized rats. Neurotransmission was temporarily inhibited by bilateral microinjection of the nonselective synapse blocker CoCl(2) in the LSA. Bilateral microinjection of 100 nL of 1 mM CoCl(2) into the LSA did not affect blood pressure or heart rate baseline, suggesting no tonic LSA influence on resting cardiovascular parameters. However, 10 min after CoCl(2) microinjections, maximum tachycardiac responses to blood pressure decreases caused by intravenous infusion of sodium nitroprusside and bradycardiac responses evoked by blood pressure increases caused by intravenous infusion of phenylephrine were enhanced when compared with control values. These enhancement of both the tachycardiac and bradycardiac reflex evoked increase of baroreflex gain. Baroreflex activity returned to control values 60 min after CoCl(2) microinjections, confirming the reversible blockade. The present results indicate an involvement of the LSA in baroreflex modulation. Data suggest that synapses in the LSA play a tonic inhibitory influence on both the sympathetic and the parasympathetic components of the baroreflex in unanesthetized rats.