β2-adrenoceptor-mediated facilitation of glutamatergic transmission in rat ventromedial hypothalamic neurons

Lee, J.-G.; Choi, In Sun; Park, E.-J.; Cho, J.-H.; Lee, M.-G.; Choi, Byung Jin; Jang, Il‐Sung

doi:10.1016/j.neuroscience.2006.10.049

Cited by 15 publications

(13 citation statements)

References 54 publications

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“…Taken together, our data suggest that norepinephrine release into the VMH during hypoglycemia acts to promote glucose recovery, at least in part via stimulation of B2AR. These findings are consistent with previous studies showing that norepinephrine activates isolated glutamatergic neurons derived from the rat VMH via B2AR (11). …”

Section: Discussionsupporting

confidence: 93%

“…In contrast, blockade of VMH B1AR or B3AR failed to have a significant inhibitory effect on counterregulatory responses. It should be noted that for these studies we used similar concentrations of BAR agonists and antagonists (1 μmol/L) as were used in previous in vivo (12,20) and in vitro (11) studies examining the specific receptors mediating the effects of norepinephrine on VMH neurons. Although these concentrations exceed the nanomolar norepinephrine concentrations present in the VMH interstitial fluid, if one takes into account the dilution of the agent in the VMH and in vivo clearance from the tissue during the study, the active local dose level in the VMH was considerably lower.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, monoamine neurotransmitters, such as norepinephrine, are also released into the VMH and appear to regulate VMH function during hypoglycemia. It has been reported that norepinephrine has been reported to stimulate glutamatergic neurotransmission in mechanically dissociated rat VMH neurons and that this effect is mediated via activation of β 2 -adrenergic receptors (B2AR) (11). The loss of function of glutamatergic neurons in the VMH region, however, suppresses glucose counterregulation in mice (10).…”

mentioning

confidence: 99%

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Modulation of β-Adrenergic Receptors in the Ventromedial Hypothalamus Influences Counterregulatory Responses to Hypoglycemia

et al. 2011

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OBJECTIVENorepinephrine is locally released into the ventromedial hypothalamus (VMH), a key brain glucose-sensing region in the response to hypoglycemia. As a result, this neurotransmitter may play a role in modulating counterregulatory responses. This study examines whether norepinephrine acts to promote glucose counterregulation via specific VMH β-adrenergic receptors (BAR).RESEARCH DESIGN AND METHODSAwake male Sprague-Dawley rats received, via implanted guide cannulae, bilateral VMH microinjections of 1) artificial extracellular fluid, 2) B2AR agonist, or 3) B2AR antagonist. Subsequently, a hyperinsulinemic-hypoglycemic clamp study was performed. The same protocol was also used to assess the effect of VMH delivery of a selective B1AR or B3AR antagonist.RESULTSDespite similar insulin and glucose concentrations during the clamp, activation of B2AR in the VMH significantly lowered by 32% (P < 0.01), whereas VMH B2AR blockade raised by 27% exogenous glucose requirements during hypoglycemia (P < 0.05) compared with the control study. These changes were associated with alternations in counterregulatory hormone release. Epinephrine responses throughout hypoglycemia were significantly increased by 50% when the B2AR agonist was delivered to the VMH (P < 0.01) and suppressed by 32% with the B2AR antagonist (P < 0.05). The glucagon response was also increased by B2AR activation by 63% (P < 0.01). Neither blockade of VMH B1AR nor B3AR suppressed counterregulatory responses to hypoglycemia. Indeed, the B1AR antagonist increased rather than decreased epinephrine release (P < 0.05).CONCLUSIONSLocal catecholamine release into the VMH enhances counterregulatory responses to hypoglycemia via stimulation of B2AR. These observations suggest that B2AR agonists might have therapeutic benefit in diabetic patients with defective glucose counterregulation.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Modulation of β-Adrenergic Receptors in the Ventromedial Hypothalamus Influences Counterregulatory Responses to Hypoglycemia

et al. 2011

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“…Although few studies have examined b-adrenergic receptors in the IL, b 2 -adrenergic receptors may be located presynaptically in the IL, as autoradiography (Rainbow et al 1984;Booze et al 1989), but not in situ hybridization studies (Nicholas et al 1993), found such receptors in the mPFC. Evidence from the hypothalamus suggests that presynaptically located b 2 receptors are located on incoming glutamatergic neurons and positively modulate glutamate release (Lee et al 2007). Whether b 2 receptors have a similar role in IL circuitry in the present paradigm is unknown.…”

Section: B-adrenergic Receptorsmentioning

confidence: 75%

The infralimbic cortex regulates the consolidation of extinction after cocaine self-administration

LaLumiere¹,

Niehoff²,

Kalivas³

2010

Learn. Mem.

164

144

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The infralimbic cortex (IL) regulates the consolidation of extinction learning for fear conditioning. Whether the IL influences the consolidation of extinction learning for cocaine self-administration is unknown. To address this issue, male Sprague -Dawley rats underwent 2 wk of cocaine self-administration followed by extinction training. On the first 5 d of extinction, rats underwent brief (15-or 30-min) extinction sessions and received intra-IL microinjections immediately after each extinction session. On days 6-12 of extinction, rats underwent full-length (2-h) extinction sessions that were used to assess the retention of the extinction learning from the short sessions. IL inactivation via microinjections of the GABA agonists baclofen and muscimol (BM) immediately after the extinction sessions (days 1-5) impaired the retention of extinction learning. Control experiments demonstrated that this effect was not due to inactivation of the prelimbic cortex or due to effects of the drugs on the subsequent day's behavior. In contrast, post-training intra-IL microinjections of the allosteric AMPA receptor potentiator 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluorophenoxyacetamide (PEPA) enhanced retention of the extinction learning. As evidence suggests a role for the b-adrenergic receptors in memory consolidation, other rats received microinjections of the b 2 -adrenergic receptor agonist clenbuterol or antagonist ICI-118,551 (ICI). Post-training intra-IL administration of clenbuterol or pre-training administration of ICI enhanced or impaired, respectively, the retention of extinction learning. These data indicate that the IL, and specifically the glutamatergic and b-adrenergic systems in the IL, regulates the consolidation of extinction of cocaine self-administration and that the IL can be manipulated to influence the retention of extinction.

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“…Norepinephrine neurons originating from the brainstem as well as other hypothalamic regions that project to the VMH may be important components of the glucose-sensing network 22,57 . More recently, it was reported that norepinephrine can stimulate glutamatergic neurotransmission in mechanically dissociated rat VMH neurons and that this effect is mediated via activation of β 2 -adrenergic receptors 58 .…”

Section: Norepinephrinementioning

confidence: 99%

Influence of VMH fuel sensing on hypoglycemic responses

Chan¹,

Sherwin²

2013

Trends in Endocrinology & Metabolism

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Hypoglycemia produces complex neural and hormonal responses that restore glucose levels to normal. Glucose, metabolic substrates and their transporters, neuropeptides and neurotransmitters alter the firing rate of glucose sensing neurons in the ventromedial hypothalamus (VMH) which monitor energy status and regulate the release of neurotransmitters that instigate a suitable counterregulatory response. Under normal physiological conditions, these mechanisms maintain blood glucose concentrations within narrow margins. However, antecedent hypoglycemia and diabetes can lead to adaptations within the brain that impair counterregulatory responses. Clearly, the mechanisms employed to detect and regulate the response to hypoglycemia and the pathophysiology of defective counterregulation in diabetes are complex and need to be elucidated so therapies can be developed to prevent or reduce the risk of hypoglycemia.

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β2-adrenoceptor-mediated facilitation of glutamatergic transmission in rat ventromedial hypothalamic neurons

Cited by 15 publications

References 54 publications

Modulation of β-Adrenergic Receptors in the Ventromedial Hypothalamus Influences Counterregulatory Responses to Hypoglycemia

Modulation of β-Adrenergic Receptors in the Ventromedial Hypothalamus Influences Counterregulatory Responses to Hypoglycemia

The infralimbic cortex regulates the consolidation of extinction after cocaine self-administration

Influence of VMH fuel sensing on hypoglycemic responses

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