Differential effect of viral overexpression of nucleus accumbens shell 5-HT1B receptors on stress- and cocaine priming-induced reinstatement of cocaine seeking.

5-HT1B receptors are densely expressed on terminals of medium spiny neurons projecting from the nucleus accumbens shell (NAccSh) to the ventral tegmental area, where 5-HT1B receptors modulate GABA release directly, and firing of dopaminergic neurons indirectly. While interactions between NAccSh 5-HT1B receptors and stress have been reported in early stages of psychostimulant-induced neuroadaptations, specifically psychomotor sensitization, the effect of this interaction on later stages of drug seeking is currently unknown. Here, we examined the effect of herpes simplex virus (HSV)-mediated overexpression of NAccSh 5-HT1B receptors on reinstatement of cocaine seeking induced by exposure to stress or a cocaine prime.

5-HT(1B) autoreceptor regulation of serotonin transporter activity in synaptosomes.

Serotonin-1B (5-HT(1B) ) autoreceptors are located in serotonin (5-HT) terminals, along with serotonin transporters (SERT), and play a critical role in autoregulation of serotonergic neurotransmission and are implicated in disorders of serotonergic function, particularly emotional regulation. SERT modulates serotonergic neurotransmission by high-affinity reuptake of 5-HT. Alterations in SERT activity are associated with increased risk for depression and anxiety.

DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function.

Previous studies demonstrated decreased levels of DJ-1 and α-synuclein (αSYN) in human cerebrospinal fluid (CSF) in patients with Parkinson's disease (PD), but neither marker correlated with PD severity, raising the possibility that they may be excellent progression markers during early or preclinical phases of PD. Individuals carrying the leucine-rich repeat kinase 2 (LRRK2) gene mutation are at increased risk for PD, and the phenotype of LRRK2 patients is almost identical to sporadic PD. To determine whether dopaminergic dysfunction in the basal ganglia, as determined by positron emission tomography (PET) scans, correlates with CSF levels of DJ-1 and αSYN during preclinical stages, Luminex assays were used to analyze CSF samples from asymptomatic LRRK2 mutation carriers, along with carriers who presented with a clinical diagnosis of PD.

Salivary tau species are potential biomarkers of Alzheimer's disease.

Phosphorylation of tau protein is a critical event in the pathogenesis of Alzheimer's disease (AD). Increased phosphorylated tau and total tau levels, combined with reduced concentrations of amyloid-β 1-42 (Aβ42) in cerebrospinal fluid (CSF), but not in plasma or serum, have been generally accepted as sensitive AD diagnostic markers. However, obtaining CSF is a relatively invasive procedure that requires participation of specially trained medical professionals, i.

5-HT1B mRNA expression after chronic social stress.

Chronic stress contributes to vulnerability for depression and drug addiction. The function of the serotonergic system has been found to be modified by chronic stress and these changes may play an important role in stress-related relapses to drug craving. The 5-HT(1B) receptor is expressed in nucleus accumbens (NAc) projection neurons and modulates drug reward mechanisms and there is evidence suggesting that stress alters the regulation and function of these receptors.

Pleasurable behaviors reduce stress via brain reward pathways.

Individuals often eat calorically dense, highly palatable "comfort" foods during stress for stress relief. This article demonstrates that palatable food intake (limited intake of sucrose drink) reduces neuroendocrine, cardiovascular, and behavioral responses to stress in rats. Artificially sweetened (saccharin) drink reproduces the stress dampening, whereas oral intragastric gavage of sucrose is without effect.

Overexpression of 5-HT(1B) mRNA in nucleus accumbens shell projection neurons differentially affects microarchitecture of initiation and maintenance of ethanol consumption.

Serotonin 1B (5-HT(1B)) heteroreceptors on nucleus accumbens shell (NAcSh) projection neurons have been shown to enhance the voluntary consumption of alcohol by rats, presumably by modulating the activity of the mesolimbic reward pathway. The present study examined whether increasing 5-HT(1B) receptors expressed on NAcSh projection neurons by means of virus-mediated gene transfer enhances ethanol consumption during the initiation or maintenance phase of drinking and alters the temporal pattern of drinking behavior. Animals received stereotaxic injections of viral vectors expressing either 5-HT(1B) receptor and green fluorescent protein (GFP) or GFP alone.

The role of the forebrain glucocorticoid receptor in acute and chronic stress.

Previous work has implicated the forebrain glucocorticoid receptor (GR) in feedback regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present series of experiments used male mice with a targeted forebrain-specific GR knockout (in which forebrain includes the prefrontal cortex, hippocampus, and basolateral amygdala) to determine the role of forebrain GR in HPA axis regulation after stress. The data indicate that the forebrain GR is necessary for maintaining basal regulation of corticosterone secretion in the morning, confirming its role in HPA axis regulation.

The role of the posterior medial bed nucleus of the stria terminalis in modulating hypothalamic-pituitary-adrenocortical axis responsiveness to acute and chronic stress.

The bed nucleus of the stria terminalis (BST) plays a prominent role in brain integration of acute responses to stressful stimuli. This study tests the hypothesis that the BST plays a complementary role in regulation of physiological changes associated with chronic stress exposure. Male Sprague-Dawley rats received bilateral ibotenate lesions or sham lesions of the posterior medial region of the BST (BSTpm), an area known to be involved in inhibition of HPA axis responses to acute stress.

The anteroventral bed nucleus of the stria terminalis differentially regulates hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress.

The anteroventral region of the bed nucleus of the stria terminalis (BST) stimulates hypothalamic-pituitary-adrenocortical (HPA) axis responses to acute stress. However, the role of the anterior BST nuclei in chronic drive of the HPA axis has yet to be established. Therefore, this study tests the role of the anteroventral BST in physiological responses to chronic drive, using a chronic variable stress (CVS) model.

Bed nucleus of the stria terminalis subregions differentially regulate hypothalamic-pituitary-adrenal axis activity: implications for the integration of limbic inputs.

Limbic and cortical neurocircuits profoundly influence hypothalamic-pituitary-adrenal (HPA) axis responses to stress yet have little or no direct projections to the hypothalamic paraventricular nucleus (PVN). Numerous lines of evidence suggest that the bed nucleus of the stria terminalis (BST) is well positioned to relay limbic information to the PVN. The BST comprises multiple anatomically distinct nuclei, of which some are known to receive direct limbic and/or cortical input and to heavily innervate the PVN.

Daily limited access to sweetened drink attenuates hypothalamic-pituitary-adrenocortical axis stress responses.

Stress can promote palatable food intake, and consumption of palatable foods may dampen psychological and physiological responses to stress. Here we develop a rat model of daily limited sweetened drink intake to further examine the linkage between consumption of preferred foods and hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress. Adult male rats with free access to water were given additional twice-daily access to 4 ml sucrose (30%), saccharin (0.

Ontogeny of the adrenal response to (+)-methamphetamine in neonatal rats: the effect of prior drug exposure.

We examined the ontogeny of the corticosterone response to (+)-methamphetamine in neonatal rats. In experiment-1, animals were injected with 10 mg/kg of (+)-methamphetamine or saline and plasma corticosterone levels were examined in separate groups 30 or 105 min later on postnatal day (P) 1, 3, 5, 7, 9, 11, 13, 15, 17, or 19. The adrenal response to methamphetamine was best described by a U-shaped function with the nadir of corticosterone release occurring between P7 and P13.

Stability of neuroendocrine and behavioral responsiveness in aging Fischer 344/Brown-Norway hybrid rats.

Aging in rodents and primates is accompanied by changes in hypothalamic-pituitary-adrenal (HPA) activity. We examined behavioral and neuroendocrine responses in 3, 15-, and 30-month-old F344/Brown-Norway rats. Basal corticosterone and ACTH levels did not differ with age, although ACTH responses, but not corticosterone responses to restraint stress, were significantly lower in the 30-month-old group relative to 3- and 15-month-old rats.

Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Na(v)1.6).

Scn8a encodes an abundant, widely distributed voltage-gated sodium channel found throughout the central and peripheral nervous systems. Mice with different mutant alleles of Scn8a provide models of the movement disorders ataxia, dystonia, tremor and progressive paralysis. We previously reported that the phenotype of the hypomorphic allele of Scn8a, medJ, is dependent upon an unlinked modifier locus, Scnm1.