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Linda Rinaman

Publications and source records attributed to Linda Rinaman.

17 recordsLinked to original sources
PubMed2006

Progressive postnatal increases in Fos immunoreactivity in the forebrain and brain stem of rats after viscerosensory stimulation with lithium chloride.

Interoceptive signals have a powerful impact on the motivation and emotional learning of animals during stressful experiences. However, current insights into the organization of interoceptive pathways stem mainly from observation and manipulation of adults, and little is known regarding the functional development of viscerosensory signaling pathways. To address this, we have examined central neural activation patterns in rat pups after treatment with lithium chloride (LiCl), a malaise-inducing agent. Rat pups were injected intraperitoneally with 0.15 M LiCl or 0.15 M NaCl (2% body wt) on postnatal day (P)0, 7, 14, 21, or 28, perfused 60 to 90 min postinjection, and their brains assayed for Fos protein immunolabeling. Compared with saline treatment, LiCl increased Fos only slightly in the area postrema, nucleus of the solitary tract, and lateral parabrachial nucleus on P0. LiCl did not increase Fos above control levels in the central nucleus of the amygdala, bed nucleus of the stria terminalis (BNST), or paraventricular nucleus of the hypothalamus on P0 but did on P7 and later. Maximal Fos responses to LiCl were observed on P14 in all areas except the BNST, in which LiCl-induced Fos activation continued to increase through P28. These results indicate that central LiCl-sensitive interoceptive circuits in rats are not fully functional at birth, and show age-dependent increases in neural Fos responses to viscerosensory stimulation with LiCl.

Animals↗
PubMed2006

Noradrenergic inputs to the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus underlie hypothalamic-pituitary-adrenal axis but not hypophagic or conditioned avoidance responses to systemic yohimbine.

The alpha2 adrenoceptor antagonist yohimbine (YO) increases transmitter release from adrenergic/noradrenergic (NA) neurons. Systemic YO activates the hypothalamic-pituitary-adrenal (HPA) axis, inhibits feeding, and supports conditioned flavor avoidance (CFA) in rats. To determine whether these effects require NA inputs to the bed nucleus of the stria terminalis (BNST), vehicle or saporin toxin conjugated to an antibody against dopamine beta hydroxylase (DSAP) was microinjected bilaterally into the BNST to remove its NA inputs. Subsequent tests failed to reveal any lesion effect on the ability of YO (5.0 mg/kg, i.p.) to inhibit food intake or to support CFA. Conversely, HPA axis responses to YO were significantly blunted in DSAP rats. In a terminal experiment, DSAP and control rats were perfused 90-120 min after intraperitoneal injection of YO or vehicle. Brains were processed to reveal Fos immunolabeling and lesion extent. NA fibers were markedly depleted in the BNST and medial parvocellular paraventricular hypothalamus (PVNmp) in DSAP rats, evidence for collateralized NA inputs to these regions. DSAP rats displayed significant loss of caudal medullary NA neurons, and markedly blunted Fos activation in the BNST and in corticotropin-releasing hormone-positive PVNmp neurons after YO. We conclude that a population of medullary NA neurons provides collateral inputs to the BNST and PVNmp, and that these inputs contribute importantly to Fos expression and HPA axis activation after YO treatment. Conversely, NA-mediated activation of BNST and PVNmp neurons is unnecessary for YO to inhibit food intake or support CFA, evidence for the sufficiency of other intact neural pathways in mediating those effects.

Animals↗
PubMed2006

Ontogeny of hypothalamic-hindbrain feeding control circuits.

Ingestive behavior is a complex product of distributed central control systems that respond to a diverse array of internal and external sensory stimuli. Relatively little is known regarding the pathways and mechanisms by which relevant signals are conveyed to the neural circuits that ultimately control ingestive motor output. This report summarizes findings regarding the postnatal development of descending hypothalamic inputs to the hindbrain dorsal vagal complex (DVC). Evidence accumulated primarily in rats indicates that descending neural projections from the hypothalamus to the DVC are both structurally and functionally immature at birth. The progressive postnatal maturation of these projections occurs in parallel with newly emerging physiological and behavioral responsiveness to treatments and stimuli that affect food intake in adults. Thus, the postnatal emergence of new feeding controls may reflect the emerging access of these controls to DVC neural circuits.

Animals↗
PubMed2005

The anxiogenic drug yohimbine activates central viscerosensory circuits in rats.

Systemic administration of the alpha(2)-adrenoceptor antagonist yohimbine (YO) activates the HPA stress axis and promotes anxiety in humans and experimental animals. We propose that visceral malaise contributes to the stressful and anxiogenic effects of systemic YO and that YO recruits brainstem noradrenergic (NA) and peptidergic neurons that relay viscerosensory signals to the hypothalamus and limbic forebrain. To begin testing these hypotheses, the present study explored dose-related effects of YO on food intake, conditioned flavor avoidance (CFA), and Fos immunolabeling in rats. Systemic YO (5.0 mg/kg BW, i.p.) inhibited food intake, supported CFA, and increased Fos immunolabeling in identified NA neurons in the ventrolateral medulla, nucleus of the solitary tract, and locus coeruleus. YO also increased Fos in the majority of corticotropin releasing hormone-positive neurons in the paraventricular nucleus of the hypothalamus. YO administered at 1.0 mg/kg BW did not inhibit food intake, did not support CFA, and did not increase Fos immunolabeling. Retrograde neural tracing demonstrated that neurons activated by YO at 5.0 mg/kg BW included medullary and pontine neurons that project to the central nucleus of the amygdala and to the lateral bed nucleus of the stria terminalis, the latter region receiving comparatively greater input by Fos-positive neurons. We conclude that YO produces anorexigenic and aversive effects that correlate with activation of brainstem viscerosensory inputs to the limbic forebrain. These findings invite continued investigation of how central viscerosensory signaling pathways interact with hypothalamic and limbic regions to influence interrelated physiological and behavioral components of anxiety, stress, and visceral malaise.

Adrenergic alpha-Antagonists↗
PubMed2005

Early experience modifies the postnatal assembly of autonomic emotional motor circuits in rats.

Rat pups that are repeatedly handled and separated from their dam exhibit altered adult behavioral, endocrine, and autonomic responses to stress, but the extent to which early handling and/or maternal separation (H/S) alters the development of circuits that underlie these responses is unknown. The present study tested the hypothesis that early H/S alters the postnatal assembly of synapses within preautonomic emotional motor circuits. Circuit development was traced by synapse-dependent retrograde transneuronal transport of pseudorabies virus (PRV) from the stomach wall. Control and H/S rats were analyzed between postnatal day 6 (P6) and P10, a period of rapid synaptic assembly among preautonomic circuit components. Pups in H/S groups were removed from their dam daily for either 15 min or 3 h beginning on P1, and were injected with virus on P8 and perfused on P10. Quantitative analyses of primary and transsynaptic PRV immunolabeling confirmed an age-dependent assembly of hypothalamic, limbic, and cortical inputs to autonomic nuclei. Circuit assembly was significantly altered in H/S pups, in which fewer neurons in the central amygdala, the bed nucleus of the stria terminalis, and visceral cortices were infected compared with age-matched controls. In contrast, H/S did not alter the assembly of paraventricular hypothalamic inputs to gastric autonomic neurons. H/S-related reductions in limbic and cortical transneuronal infection were similar in pups exposed daily to 15 min or 3 h maternal separation. These findings support the view that environmental events during early postnatal life can influence the formation of neural circuits that provide limbic and cortical control over autonomic emotional motor output.

Age Factors↗
PubMed2005

Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion.

Laboratory mice drink little sucrose solution on initial exposure, but later develop a strong preference for sucrose over water that plateaus after a few days. Both the initial neophobia and later plateau of sucrose intake may involve central oxytocin (OT) signaling pathways. If so, then mice that lack the gene for OT [OT knockout (KO)] should exhibit enhanced initial and sustained sucrose intake compared with wild-type (WT) cohorts. To test this hypothesis, female OT KO and WT mice (11-13 mo old) were given a two-bottle choice between 10% sucrose and water available ad libitum for 4 days. On the first day, sucrose intake was 20-fold greater in OT KO mice compared with WT cohorts. The avid sucrose consumption by OT KO mice increased further on day 2 and was sustained at significantly higher levels than intake by WT mice. Enhanced initial and sustained sucrose intake also was observed in 5- to 7-mo-old male OT KO mice. The effect of genotype was observed over a range of sucrose concentrations and was maintained over at least 8 days of continual exposure. However, there was no effect of genotype on daily intake of sucrose-enriched powdered chow. These findings indicate that the genetic absence of OT in mice is associated with enhanced initial and sustained intake of sucrose solutions. Thus central OT pathways may normally participate in limiting initial intake of novel ingesta and may also participate in limiting intake of sweet, highly palatable familiar ingesta.

Administration, Oral↗
PubMed2005

Dehydration anorexia is attenuated in oxytocin-deficient mice.

Evidence in rats suggests that central oxytocin (OT) signaling pathways contribute to suppression of food intake during dehydration (i.e., dehydration anorexia). The present study examined water deprivation-induced dehydration anorexia in wild-type and OT -/- mice. Mice were deprived of food alone (fasted, euhydrated) or were deprived of both food and water (fasted, dehydrated) for 18 h overnight. Fasted wild-type mice consumed significantly less chow during a 60-min refeeding period when dehydrated compared with their intake when euhydrated. Conversely, fasting-induced food intake was slightly but not significantly suppressed by dehydration in OT -/- mice, evidence for attenuated dehydration anorexia. In a separate experiment, mice were deprived of water (but not food) overnight for 18 h; then they were anesthetized and perfused with fixative for immunocytochemical analysis of central Fos expression. Fos was elevated similarly in osmo- and volume-sensitive regions of the basal forebrain and hypothalamus in wild-type and OT -/- mice after water deprivation. OT-positive neurons expressed Fos in dehydrated wild-type mice, and vasopressin-positive neurons were activated to a similar extent in wild-type and OT -/- mice. Conversely, significantly fewer neurons within the hindbrain dorsal vagal complex were activated in OT -/- mice after water deprivation compared with activation in wild-type mice. These findings support the view that OT-containing projections from the hypothalamus to the hindbrain are necessary for the full expression of compensatory behavioral and physiological responses to dehydration.

Animals↗
PubMed2005

Trimethylthiazoline supports conditioned flavor avoidance and activates viscerosensory, hypothalamic, and limbic circuits in rats.

Interoceptive stimuli modulate stress responses and emotional state, in part, via ascending viscerosensory inputs to the hypothalamus and limbic forebrain. It is unclear whether similar viscerosensory pathways are recruited by emotionally salient exteroceptive stimuli, such as odors. To address this question, we investigated conditioned avoidance and central c-Fos activation patterns in rats exposed to synthetic trimethylthiazoline (TMT), an odiferous natural component of fox feces. Experiment 1 demonstrated that rats avoid consuming novel flavors that previously were paired with TMT exposure, evidence that TMT supports conditioned flavor avoidance. Experiment 2 examined central neural systems activated by TMT. Odor-naive rats were acutely exposed to low or high levels of TMT or a novel nonaversive control odor and were perfused with fixative 60-90 min later. A subset of rats received retrograde neural tracer injections into the central nucleus of the amygdala (CeA) 7-10 days before odor exposure and perfusion. Brain sections were processed for dual-immunocytochemical detection of c-Fos and other markers to identify noradrenergic (NA) neurons, corticotropin-releasing hormone (CRH) neurons, and retrogradely labeled neurons projecting to the CeA. Significantly greater proportions of medullary and pontine NA neurons, hypothalamic CRH neurons, and CeA-projecting neurons were activated in rats exposed to TMT compared with activation in rats exposed to the nonaversive control odor. Thus the ability of TMT to support conditioned avoidance behavior is correlated with significant odor-induced recruitment of hypothalamic CRH neurons and brain stem viscerosensory inputs to the CeA.

Amygdala↗
PubMed2004

The role of central glucagon-like peptide-1 in mediating the effects of visceral illness: differential effects in rats and mice.

In rats, central administration of glucagon-like peptide-1 (GLP-1) elicits symptoms of visceral illness like those caused by the toxin lithium chloride (LiCl), including anorexia, conditioned taste aversion (CTA) formation, and neural activation in the hypothalamus and hindbrain including activation of brainstem preproglucagon cells. Most compellingly, pharmacological antagonists of the GLP-1 receptor (GLP-1R) block several effects of LiCl in rat. The major goal of these experiments was to further test the hypothesis that the central nervous system GLP-1 system is critical to the visceral illness actions of LiCl by using mice with a targeted disruption of the only described GLP-1R. First, we observed that, like the rat, LiCl activates preproglucagon neurons in wild-type mice. Second, GLP-1R -/- mice demonstrated normal anorexic and CTA responses to LiCl. To test the possibility that alternate GLP-1Rs mediate aversive effects, we examined the ability of GLP-1 to produce a CTA in GLP1R -/- mice. Although lateral ventricular GLP-1 produced a CTA in wild-type mice, it did not produce a CTA in GLP-1R -/- mice. Furthermore, the same GLP-1R antagonist that can block the aversive effects of LiCl in the rat failed to do so in the mouse. These results support the conclusion that in mouse, unlike in rat, GLP-1R signaling is not required for the visceral illness response to LiCl. Such species differences are an important consideration when comparing results from rat and mouse studies.

Animals↗
PubMed2004

Enhanced corticosterone concentrations and attenuated Fos expression in the medial amygdala of female oxytocin knockout mice exposed to psychogenic stress.

Centrally released oxytocin (OT) is believed to attenuate the response of the hypothalamic-pituitary-adrenal (HPA) axis to psychogenic stress. To test this hypothesis, we measured plasma corticosterone concentrations and Fos-immunoreactive protein in the paraventricular nucleus of the hypothalamus (PVN) and limbic brain areas of female wild-type and OT knockout mice that were exposed to a shaker platform, a predominantly psychogenic stress. Plasma corticosterone concentrations after shaker stress were higher in female OT knockout mice than wild-type mice. Genotypic differences in the corticosterone response after shaker stress persisted across all stages of the estrous cycle and when mice were conditioned to repeated shaker stress. Shaker stress activated Fos in OT-positive neurons of wild-type mice and corticotropin-releasing hormone-positive, but not vasopressin-positive, neurons within the PVN of wild-type and OT knockout mice. Fos expression was also increased after shaker stress in the bed nucleus of the stria terminalis, medial and central nuclei of the amygdala, medial preoptic area, and the paraventricular nucleus of the thalamus of wild-type and OT knockout mice. However, Fos expression in the medial amygdala was significantly lower in female OT knockout mice than wild-type mice. Our findings indicate heightened stress-induced corticosterone release in female OT knockout mice. Therefore, the results suggest that OT pathways play a role in attenuating the HPA axis response to psychogenic stress in female mice.

Amygdala↗
PubMed2004

Anterograde transneuronal viral tracing of central viscerosensory pathways in rats.

Previous studies demonstrated that strain H129 of herpes simplex virus-1 undergoes anterograde transneuronal transport in mice and primates after peripheral or central injection. In this study, H129 was used in rats to identify CNS regions that receive relayed viscero-sensory inputs from the stomach wall. We also examined whether transneuronal viral transport in this model is exclusively anterograde. H129 or an established retrograde transneuronal viral tracer, pseudorabies virus (PRV), was injected into the ventral stomach wall in intact rats or in rats with previous subdiaphragmatic vagal sensory deafferentation. Rats were perfused with fixative 3-5 d later, and tissues were processed for immunocytochemical detection of transported virus. In intact rats, H129 was transported transneuronally via vagal and spinal viscerosensory neurons to postsynaptic target cells in the medullary dorsal vagal complex and thoracic dorsal horn, respectively, with subsequent transport to discrete regions of the medullary and pontine reticular formation, cerebellum, parabrachial nucleus, periaqueductal gray, thalamus, hypothalamus, amygdala, bed nucleus of the stria terminalis, and other central sites. Comparison of labeling patterns in intact and vagal deafferented rats indicated that H129 also produced first-order retrograde infection of autonomic neurons that project directly to virus injection sites, similar to PRV. Unlike PRV, however, H129 was not transported transneuronally in the retrograde direction from infected neurons to central sources of presynaptic input. We conclude that transneuronal transport of H129 occurs exclusively in the anterograde direction to reveal CNS regions that receive direct and relayed viscerosensory signals.

Afferent Pathways↗
PubMed2003

Hindbrain noradrenergic lesions attenuate anorexia and alter central cFos expression in rats after gastric viscerosensory stimulation.

Behavioral, autonomic, and endocrine outputs of the CNS are subject to important feedback modulation by viscerosensory signals that are conveyed initially to the hindbrain nucleus of the solitary tract (NST). In the present study, noradrenergic (NA) neurons [i.e., those that express the NA synthetic enzyme dopamine beta hydroxylase (DbH)] in the caudal NST were lesioned to determine their role in mediating anorexic responses to gastric stimulation and in conveying gastric sensory signals to the hypothalamus and amygdala. For this purpose, saporin toxin conjugated to an antibody against DbH was microinjected bilaterally into the caudal NST in adult rats. Control rats received similar microinjections of vehicle. Several weeks later, rats were tested for the ability of systemic cholecystokinin octapeptide (CCK) (0 or 10 microg/kg) to inhibit food intake. CCK-induced anorexia was significantly attenuated in toxin-treated rats. Rats subsequently were used in a terminal cFos study to determine central neural activation patterns after systemic CCK or vehicle and to evaluate lesion extent. Toxin-induced loss of DbH-positive NST neurons was positively correlated with loss of CCK-induced anorexia. Hypothalamic cFos expression was markedly attenuated in lesioned rats after CCK treatment, whereas CCK-induced neural activation in the parabrachial nucleus and amygdala appeared normal. These findings suggest that hindbrain NA neurons are an integral component of brainstem circuits that mediate CCK-induced anorexia and also are necessary for hypothalamic but not parabrachial or amygdala responses to gastric sensory stimulation.

Amygdala↗
PubMed2003

Postnatal development of hypothalamic inputs to the dorsal vagal complex in rats.

The hypothalamus is critically involved in energy homeostasis and is an appropriate focus for research investigating the central neural underpinnings of obesity, anorexia and normal food intake. However, little is known regarding pathways and mechanisms that convey relevant hypothalamic signals to the brainstem circuits that ultimately control ingestive behavior. This brief review highlights work investigating the postnatal development of hypothalamic inputs to the hindbrain dorsal vagal complex (DVC). Research findings indicate that these inputs are both structurally and functionally immature in newborn rats. The progressive postnatal maturation of descending projections to the DVC occurs in concert with newly emerging physiological and behavioral responses to osmotic dehydration, which inhibits gastric emptying and food intake in adult animals but not in neonates. The postnatal emergence of other intake controls might also reflect progressive engagement of DVC neural circuits, whose intrinsic components and output pathways are envisioned as being critical for initiating and terminating ingestive behavior.

Aging↗
PubMed2003

Cholecystokinin and D-fenfluramine inhibit food intake in oxytocin-deficient mice.

Results from previous studies indicate that oxytocin (OT)-containing neural pathways are activated in laboratory rats after systemic administration of CCK or d-fenfluramine and that centrally released OT may participate in the anorexigenic effects of these treatments. To explore the relationship between feeding behavior and OT function, the effects of CCK and d-fenfluramine on feeding and central c-Fos expression were compared in wild-type (OT+/+) and OT-deficient mice (OT-/-) of C57BL/6 background. Male OT+/+ and OT-/- mice were administered saline or CCK (1, 3, or 10 microg/kg ip) after overnight food deprivation. Saline-treated OT+/+ and OT-/- mice consumed equivalent amounts of food after an overnight fast. CCK inhibited deprivation-induced food intake in a dose-dependent manner to a similar extent in both genotypes. CCK treatment also induced similar hindbrain and forebrain patterns of increased c-Fos expression in mice of both genotypes. After treatment with d-fenfluramine (10 mg/kg ip), both OT+/+ and OT-/- mice consumed significantly less food than untreated controls, with no difference between genotypes. We conclude that OT signaling pathways are unnecessary for the anorexigenic effects of systemically administered CCK and d-fenfluramine in C57BL/6 mice.

Animals↗
PubMed2002

Viscerosensory activation of noradrenergic inputs to the amygdala in rats.

Norepinephrine (NE) acts in the amygdala to regulate processes underlying acquisition and expression of emotional learning. The present study investigated whether stimulation of gastric vagal sensory afferents activates neurons immunoreactive for the NE synthetic enzyme, dopamine beta hydroxylase (DbetaH), in medullary and pontine cell groups that innervate the central nucleus of the amygdala (CeA) in rats. To identify such neurons, retrograde neural tracers were microinjected bilaterally into the CeA. Seven to 10 days later, rats were injected intraperitoneally with saline vehicle (controls) or cholecystokinin octapeptide (CCK, 10 microgram/kg) to stimulate gastric vagal afferents, then perfused with fixative 60-90 min later. Brain sections were processed for localization of neural tracer and cFos protein (to identify activated cells). Approximately 30% of retrogradely labeled neurons in the nucleus of the solitary tract (NST, A2/C2 region) and 19% of retrogradely labeled neurons in the ventrolateral medulla (VLM, A1/C1 region) were activated in rats after CCK treatment. Triple immunolabeling of cFos, neural tracer, and DbetaH confirmed that the large majority of activated, CeA-projecting neurons were noradrenergic (or adrenergic). Conversely, CCK activated less than 4% of CeA-projecting neurons in the locus coeruleus (LC, A6 cell group), similar to control cases. These findings suggest that vagal afferent stimulation may modify amygdalar processes of emotional learning via direct noradrenergic/adrenergic projections from the caudal medulla to the CeA.

Amygdala↗
PubMed2002

GLP-1 receptor signaling contributes to anorexigenic effect of centrally administered oxytocin in rats.

The present study examined possible interactions between central glucagon-like peptide-1 (GLP-1) and oxytocin (OT) neural systems by determining whether blockade of GLP-1 receptors attenuates OT-induced anorexia and vice versa. Male rats were acclimated to daily 4-h food access. In the first experiment, rats were infused centrally with GLP-1 receptor antagonist or vehicle, followed by an anorexigenic dose of synthetic OT. Access to food began 20 min later. Cumulative food intake was measured every 30 min for 4 h. In the second experiment, rats were infused with OT receptor blocker or vehicle, followed by synthetic GLP-1 [(7-36) amide]. Subsequent food intake was monitored as before. The anorexigenic effect of OT was eliminated in rats pretreated with the GLP-1 receptor antagonist. Conversely, GLP-1-induced anorexia was not affected by blockade of OT receptors. In a separate immunocytochemical study, OT-positive terminals were found closely apposed to GLP-1-positive perikarya, and central infusion of OT activated c-Fos expression in GLP-1 neurons. These findings implicate endogenous GLP-1 receptor signaling as an important downstream mediator of anorexia in rats after activation of central OT neural pathways.

Animals↗