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?-Adrenergic receptors enhance excitatory transmission in the bed nucleus of the stria terminalis through a corticotrophin-releasing factor receptor-dependent and cocaine-regulated mechanism.

ABSTRACT: Evidence suggests that the noradrenergic and corticotrophin-releasing factor (CRF) systems play critical roles in relapse and stress-related behaviors. In particular, behavioral studies point to a serial signaling process initiated by ?-adrenergic receptors that requires CRF receptor (CRFR)-dependent signaling in the bed nucleus of the stria terminalis (BNST) to produce stress-induced relapse to cocaine seeking.We used whole cell patch clamp recordings from acutely prepared mouse brain slices to examine the actions of ?-adrenergic receptors and CRFR1 on excitatory transmission in BNST. We examined the effects of agonists of these receptors in slices prepared from naive, sham, and cocaine-conditioned mice.?(1)-adrenergic receptor activation within the BNST produces an enhancement of excitatory synaptic transmission that requires CRFR1-dependent signaling. We show that chronic cocaine administration transiently disrupts ?(1)-adrenergic- and CRFR1-dependent enhancement of glutamatergic transmission, that this disruption wanes with time, and that it can be reintroduced with a cocaine challenge.In total, these studies identify a circuit mechanism within the BNST that may play an important role in CRF- and norepinephrine-regulated behaviors.

SUBMITTER: Nobis WP

PROVIDER: S-EPMC3090515 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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β-Adrenergic receptors enhance excitatory transmission in the bed nucleus of the stria terminalis through a corticotrophin-releasing factor receptor-dependent and cocaine-regulated mechanism.

Nobis William P WP Kash Thomas L TL Silberman Yuval Y Winder Danny G DG

Biological psychiatry 20110221 11

<h4>Background</h4>Evidence suggests that the noradrenergic and corticotrophin-releasing factor (CRF) systems play critical roles in relapse and stress-related behaviors. In particular, behavioral studies point to a serial signaling process initiated by β-adrenergic receptors that requires CRF receptor (CRFR)-dependent signaling in the bed nucleus of the stria terminalis (BNST) to produce stress-induced relapse to cocaine seeking.<h4>Methods</h4>We used whole cell patch clamp recordings from acu ...[more]

PMID: 21334600

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Project description:BACKGROUND:The bed nucleus of the stria terminalis (BNST) contains the highest density of corticotropin-releasing factor (CRF)-producing neurons in the brain. CRF-immunoreactive neurons show a female-biased sexual dimorphism in the dorsolateral BNST in the rat. Since CRF neurons cannot be immunostained clearly with available CRF antibodies in the mouse, we used a mouse line, in which modified yellow fluorescent protein (Venus) was inserted to the CRF gene, and the Neo cassette was removed, to examine the morphological characteristics of CRF neurons in the dorsolateral BNST. Developmental changes of CRF neurons were examined from postnatal stages to adulthood. Gonadectomy (GDX) was carried out in adult male and female mice to examine the effects of sex steroids on the number of CRF neurons in the dorsolateral BNST. METHODS:The number of Venus-expressing neurons, stained by immunofluorescence, was compared between male and female mice over the course of development. GDX was carried out in adult mice. Immunohistochemistry, in combination with Nissl staining, was carried out, and the effects of sex or gonadal steroids were examined by estimating the number of Venus-expressing neurons, as well as the total number of neurons or glial cells, in each BNST subnucleus, using a stereological method. RESULTS:Most Venus-expressing neurons co-expressed Crf mRNA in the dorsolateral BNST. They constitute a group of neurons without calbindin immunoreactivity, which makes a contrast to the principal nucleus of the BNST that is characterized by calbindin immunostaining. In the dorsolateral BNST, the number of Venus-expressing neurons increased across developmental stages until adulthood. Sexual difference in the number of Venus-expressing neurons was not evident by postnatal day 5. In adulthood, however, there was a significant female predominance in the number of Venus expressing neurons in two subnuclei of the dorsolateral BNST, i.e., the oval nucleus of the BNST (ovBNST) and the anterolateral BNST (alBNST). The number of Venus-expressing neurons was smaller significantly in ovariectomized females compared with proestrous females in either ovBNST or alBNST, and greater significantly in orchiectomized males compared with gonadally intact males in ovBNST. The total number of neurons was also greater significantly in females than in males in ovBNST and alBNST, but it was not affected by GDX. CONCLUSION:Venus-expressing CRF neurons showed female-biased sexual dimorphism in ovBNST and alBNST of the mouse. Expression of Venus in these subnuclei was controlled by gonadal steroids.

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?-Adrenergic receptors enhance excitatory transmission in the bed nucleus of the stria terminalis through a corticotrophin-releasing factor receptor-dependent and cocaine-regulated mechanism.

Publications

β-Adrenergic receptors enhance excitatory transmission in the bed nucleus of the stria terminalis through a corticotrophin-releasing factor receptor-dependent and cocaine-regulated mechanism.

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