Effect of dorsomedial hypothalamic nuclei knife cuts on ingestive behavior.
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Previous findings show that rats with electrolytic or excitotoxic lesions in the dorsomedial hypothalamic nucleus (DMN) are hypophagic and hypodipsic and have reduced ponderal and linear growth but normal body composition. DMN-lesioned (DMNL) rats also show altered ingestive responses to naloxone. The present study investigated the intrahypothalamic nerve pathways involved in these DMNL effects and the response of the pathways to deprivation challenges by placing knife cuts posterior (Post), lateral (Lat), ventral (Vent), dorsal, or anterior to the DMN or by administering sham operations. One major finding was that rats with Post or Vent were hypophagic (P < 0. 05) and had reduced body weight but responded normally to deprivation challenges. Post and Lat groups were hypodipsic (P < 0. 05), but plasma Na+, K+, and osmolality and 24-h post-water-deprivation drinking responses were similar in all groups. Naloxone did not suppress the intake of Post rats. It appears that the hypophagia and the reduced body weight after DMNL involve fibers entering or leaving the DMN from ventral and posterior directions, and they may be part of an opioid feeding system. (+info)
Effects of dorsomedial hypothalamic nuclei lesions on intake of an imbalanced amino acid diet.
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Within 3 h of ingesting an imbalanced amino acid diet (Imb), rats show attenuated intake, which can be ameliorated by prior administration of the serotonin receptor antagonist tropisetron (Trop). Earlier work in which the dorsomedial hypothalamic nucleus (DMN) was electrolytically lesioned (DMNL) determined that this structure plays a role in the early detection of and subsequent adaptation to Imb. However, that study did not address whether cell bodies in the DMN, fibers of passage, or both were involved in the DMNL response to Imb. In the present investigation in experiment 1, rats were given electrolytic DMNL or a sham operation (Sham). The rats were injected with saline (Sal) or Trop just before introduction of Imb. By 3 h Sal-DMNL rats consumed more Imb than did the Sal-Sham rats; intake was normal by 12 h. Trop enhanced Imb intake, with Trop and DMNL being additive. By day 4 the DMNL rats were eating and gaining weight less than were Sham rats. In experiment 2, DMN cell bodies were destroyed by ibotenic acid (Ibo). Sal-injected Ibo-lesioned and Sham rats showed similar food intake depression on Imb; Trop similarly increased Imb intake in both groups. By day 4 both Ibo-L rats were eating and gaining weight less than were Sham rats. In experiment 3, groups of rats were given knife cuts posterior, lateral, ventral, dorsal, or anterior to the DMN. During the first 3 h of consuming Imb, all cuts except posterior enhanced the intake of Imb. Over the next 24 h the anterior cut group continued to eat more Imb than did the Sham rats. In experiment 4 DMNL rats were given novel diets; the DMNL rats did not display a neophilic response. The data suggest that fiber tracts that pass through the DMN may be involved in the early detection of Imb. DMN cell bodies, or fibers of passage, are not involved in the Trop effect. Finally, DMN cell bodies are necessary for proper long-term adaptation to Imb. (+info)
Hypothalamopontine projections in the rat: anterograde axonal transport studies utilizing light and electron microscopy.
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Projections to the basilar pontine nuclei (BPN) from a variety of hypothalamic nuclei were traced in the rat utilizing the anterograde transport of biotinylated dextran amine. Light microscopy revealed that the lateral hypothalamic area (LH), the posterior hypothalamic area (PH), and the medial and lateral mammillary nuclei (MMN and LMN) are the four major hypothalamic nuclei that give rise to labeled fibers and terminals reaching the rostral medial and dorsomedial BPN subdivisions. Hypothalamopontine fibers extended caudally through the pontine tegmentum dorsal to the nucleus reticularis tegmenti pontis and then coursed ventrally from the main descending bundle toward the ipsilateral basilar pontine gray. Some hypothalamopontine fibers crossed the midline in the tegmental area just dorsal to the pontine gray to terminate in the contralateral BPN. Electron microscopy revealed that the ultrastructural features of synaptic boutons formed by axons arising in the LH, PH, MMN, and LMN are similar to one another. All labeled hypothalamopontine axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions with dendritic shafts as well as dendritic appendages, and occasionally with neuronal somata. Some labeled boutons formed the central axon terminal in a glomerular synaptic complex. In summary, the present findings indicate that the hypothalamus projects predominantly to the rostral medial and dorsomedial portions of the BPN which, in turn, provide input to the paraflocculus and vermis of the cerebellum. Since the hypothalamic projection zones in the BPN also receive cerebral cortical input, including limbic-related cortex, the hypothalamopontine system might serve to integrate autonomic or limbic-related functions with movement or somatic motor-related activity. Alternatively, since the cerebellum also receives direct input from the hypothalamus, the BPN may function to provide additional somatic and visceral inputs that are used by the cerebellum to perform the integrative function. (+info)
Role of the dorsomedial hypothalamus in mediating the response to benzodiazepines on trial 2 in the elevated plus-maze test of anxiety.
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Trial 2 in the elevated plus-maze provides an animal model of specific phobia (fear of heights). On this trial, rats no longer respond to benzodiazepines. The present experiment examined the role of the dorsomedial hypothalamus in mediating insensitivity to chlordiazepoxide on trial 2. Rats received a 5 min exposure to the maze, undrugged. Forty-eight hours later, rats injected with control infusions into the dorsomedial hypothalamus showed the usual lack of response to chlordiazepoxide (5 mg/kg, i.p.). However, those receiving lidocaine injections (40 micrograms/microliter in a volume of 0.2 microliter) in the dorsomedial hypothalamus (producing functional inactivation), immediately before trial 2, responded with an anxiolytic response to chlordiazepoxide, characterised by an increased percentage of time on the open arms and by an increased number of entries into, and time spent on, the distal portions of the open arms. Since the lidocaine injections were without anxiolytic effects, our results suggest that this region of the hypothalamus regulates the functional state of benzodiazepine receptors in other brain regions. (+info)
Descending pathways mediating cardiovascular response from dorsomedial hypothalamic nucleus.
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Physiological and anatomic methods were used to determine whether neurons in the rostral ventrolateral medulla (RVLM), nucleus tractus solitarius (NTS), or hypothalamic paraventricular nucleus (PVN) mediate the cardiovascular response evoked from the dorsomedial hypothalamic nucleus (DMH), which is believed to play a key role in mediating responses to stress. In urethane-anesthetized rats, activation of neurons in the DMH by microinjection of bicuculline resulted in a large increase in arterial pressure, heart rate, and renal sympathetic nerve activity. The pressor and sympathoexcitatory responses, but not the tachycardic response, were greatly reduced after bilateral muscimol injections into the RVLM even when baseline arterial pressure was maintained at a constant level. These responses were not reduced by muscimol injections into the PVN or NTS. Retrograde tracing experiments identified many neurons in the DMH that projected directly to the RVLM. The results indicate that the vasomotor and cardiac components of the response evoked from the DMH are mediated by pathways that are dependent and independent, respectively, of neurons in the RVLM. (+info)
Smelling of odorous sex hormone-like compounds causes sex-differentiated hypothalamic activations in humans.
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The anatomical pathways for processing of odorous stimuli include the olfactory nerve projection to the olfactory bulb, the trigeminal nerve projection to somatosensory and insular cortex, and the projection from the accessory olfactory bulb to the hypothalamus. In the majority of tetrapods, the sex-specific effects of pheromones on reproductive behavior is mediated via the hypothalamic projection. However, the existence of this projection in humans has been regarded as improbable because humans lack a discernable accessory olfactory bulb. Here, we show that women smelling an androgen-like compound activate the hypothalamus, with the center of gravity in the preoptic and ventromedial nuclei. Men, in contrast, activate the hypothalamus (center of gravity in paraventricular and dorsomedial nuclei) when smelling an estrogen-like substance. This sex-dissociated hypothalamic activation suggests a potential physiological substrate for a sex-differentiated behavioral response in humans. (+info)
Stimulation of P2Y1 receptors causes anxiolytic-like effects in the rat elevated plus-maze: implications for the involvement of P2Y1 receptor-mediated nitric oxide production.
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The widespread and abundant distribution of P2Y receptors in the mammalian brain suggests important functions for these receptors in the CNS. To study a possible involvement of the P2Y receptors in the regulation of fear and anxiety, the influences of the P2Y(1,11,12) receptor-specific agonist adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS), the P2X(1,3) receptor agonist alpha,beta-methylene ATP (alpha,betameATP), the unspecific P2 receptor antagonist pyridoxalphosphate-6-azopheny l-2',4'-disulfonic acid (PPADS), and the specific P2Y(1) receptor antagonist N(6)-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS 2179) on the elevated plus-maze behavior of the rat were investigated. All tested compounds were given intracerebroventricularly (0.5 microl). ADPbetaS (50 and 500 fmol) produced an anxiolytic-like behavioral profile reflected by an increase of the open arm exploration. The anxiolytic-like effects were antagonized by pretreatment with PPADS (5 pmol) or MRS 2179 (5 pmol). Both compounds caused anxiogenic-like effects when given alone. Furthermore, the anxiolytic-like effects of ADPbetaS could be antagonized by pretreatment with the nitric oxide synthase (NOS) inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME). In addition, the anxiogenic-like effects of PPADS were reversed by the pretreatment with L-arginine (500 pmol), which is the natural substrate for NOS, but not by D-arginine (500 pmol), which is not. Immunofluorescence staining revealed the presence of P2Y(1) receptors on neurons in different brain regions such as hypothalamus, amygdala, hippocampus and the periaqueductal gray. Furthermore, the colocalization of P2Y(1) receptors and neuronal NOS (nNOS) on some neurons in these regions could be demonstrated. The highest density of P2Y(1)- and nNOS-immunoreactivity was detected in the dorsomedial hypothalamic nucleus. Taken together, the present results suggest that P2Y(1) receptors are involved in the modulation of anxiety in the rat. The anxiolytic-like effects after stimulation of P2Y(1) receptors seem to be in close connection with the related nitric oxide production. (+info)
Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats.
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Rats selectively bred to develop diet-induced obesity (DIO) spontaneously gain more body weight between 5 and 7 wk of age than do those bred to be diet resistant (DR). Here, chow-fed DIO rats ate 9% more and gained 19% more body weight from 5 to 6 wk of age than did DR rats but had comparable leptin and insulin levels. However, 6-wk-old DIO rats had 29% lower plasma ghrelin levels at dark onset but equivalent levels 6 h later compared with DR rats. When subsequently fed a high-energy (HE; 31% fat) diet for 10 days, DIO rats ate 70% more, gained more body and adipose depot weight, had higher leptin and insulin levels, and had 22% lower feed efficiency than DR rats fed HE diet. In DIO rats on HE diet, leptin levels increased significantly at 3 days followed by increased insulin levels at 7 days. These altered DIO leptin and ghrelin responses were associated with 10% lower leptin receptor mRNA expression in the arcuate (ARC), dorsomedial (DMN), and ventromedial hypothalamic nuclei and 13 and 15% lower ghrelin receptor (GHS-R) mRNA expression in the ARC and DMN than in the DR rats. These data suggest that increased ghrelin signaling is not a proximate cause of DIO, whereas reduced leptin sensitivity might play a causal role. (+info)