Increased anxiety in corticotropin-releasing factor type 2 receptor-null mice requires recent acute stress exposure and is associated with dysregulated serotonergic activity in limbic brain areas.

Background: Corticotropin-releasing factor type 2 receptors (CRFR2) are suggested to facilitate successful recovery from stress to maintain mental health. They are abundant in the midbrain raphe nuclei, where they regulate serotonergic neuronal activity and have been demonstrated to mediate behavioural consequences of stress. Here, we describe behavioural and serotonergic responses consistent with maladaptive recovery from stressful challenge in CRFR2-null mice.

Chronic activation of corticotropin-releasing factor type 2 receptors reveals a key role for 5-HT1A receptor responsiveness in mediating behavioral and serotonergic responses to stressful challenge.

Background: The corticotropin-releasing factor type 2 receptor (CRFR2) is suggested to play an important role in aiding recovery from acute stress, but any chronic effects of CRFR2 activation are unknown. CRFR2 in the midbrain raphé nuclei modulate serotonergic activity of this key source of serotonin (5-HT) forebrain innervation.

Methods: Transgenic mice overexpressing the highly specific CRFR2 ligand urocortin 3 (UCN3OE) were analyzed for stress-related behaviors and hypothalamic-pituitary-adrenal axis responses.

Sex influences the effect of a lifelong increase in serotonin transporter function on cerebral metabolism.

Polymorphic variation in the human serotonin transporter (SERT; 5-HTT) gene resulting in a lifelong increase in SERT expression is associated with reduced anxiety and a reduced risk of affective disorder. Evidence also suggests that sex influences the effect of this polymorphism on affective functioning. Here we use novel transgenic mice overexpressing human SERT (hSERT OVR) to investigate the possible influence of sex on the alterations in SERT protein expression and cerebral function that occur in response to increased SERT gene transcription.

Novel analysis for improved validity in semi-quantitative 2-deoxyglucose autoradiographic imaging.

The original [(14)C]-2-deoxyglucose autoradiographic imaging technique allows for the quantitative determination of local cerebral glucose utilisation (LCMRglu) [Sokoloff L, Reivich, M, Kennedy C, Desrosiers M, Patlak C, Pettigrew K, et al. The 2-deoxyglucose-C-14 method for measurement of local cerebral glucose utilisation-theory, procedure and normal values in conscious and anestherized albino rats. J Neurochem 1977;28:897-916].

Increased expression of the 5-HT transporter confers a low-anxiety phenotype linked to decreased 5-HT transmission.

A commonly occurring polymorphic variant of the human 5-hydroxytryptamine (5-HT) transporter (5-HTT) gene that increases 5-HTT expression has been associated with reduced anxiety levels in human volunteer and patient populations. However, it is not known whether this linkage between genotype and anxiety relates to variation in 5-HTT expression and consequent changes in 5-HT transmission. Here we test this hypothesis by measuring the neurochemical and behavioral characteristics of a mouse genetically engineered to overexpress the 5-HTT.

Persistent cerebrovascular effects of MDMA and acute responses to the drug.

Acutely, 3,4,-methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [Quate et al., (2004)Psychopharmacol., 173, 287-295].

Memory reconsolidation: sensitivity of spatial memory to inhibition of protein synthesis in dorsal hippocampus during encoding and retrieval.

Reconsolidation is a putative neuronal process in which the retrieval of a previously consolidated memory returns it to a labile state that is once again subject to stabilization. This study explored the idea that reconsolidation occurs in spatial memory when animals retrieve memory under circumstances in which new memory encoding is likely to occur. Control studies confirmed that intrahippocampal infusions of anisomycin inhibited protein synthesis locally and that the spatial training protocols we used are subject to overnight protein synthesis-dependent consolidation.

Effects of a single dose of 3,4-methylenedioxymethamphetamine on circadian patterns, motor activity and sleep in drug-naive rats and rats previously exposed to MDMA.

Rationale: Despite the well documented neurochemical actions of 3,4-methylenedioxymethamphetamine (MDMA), acute effects in rats previously exposed to the drug have not been extensively explored.

Objective: To examine motor activity and vigilance effects of MDMA in drug-naive rats and in rats exposed to the drug 3 weeks earlier.

Methods: MDMA (15 mg/kg, i.

Acute methylenedioxymethamphetamine administration: effects on local cerebral blood flow and glucose utilisation in the Dark Agouti rat.

Rationale: Clinical reports indicate that acute exposure to 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") may induce pathological cerebrovascular responses in human users of the drug, however, the mechanism by which MDMA might effect these pathological changes is not clear.

Objectives: To examine the effects of acute MDMA administration on the relationship between local cerebral blood flow (LCBF) and local cerebral glucose utilisation (LCMRglu); to determine the effect, if any, acute exposure to MDMA has on the cerebral circulation, independently of alterations in cerebral metabolic demand.

Methods: Dark Agouti rats were injected with 15 mg.

Comparison of effects of MgCl2 and Gpp(NH)p on antagonist and agonist radioligand binding to adenosine A1 receptors.

Aim: To investigate modulation of antagonist and agonist binding to adenosine A1 receptors by MgCl2 and 5 -guanylimidodiphosphate (Gpp(NH)p) using rat brain membranes and the A1 antagonist [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and the A1 agonist [3H]-2-chloro-N6-cyclopentyladenosine ([3H]CCPA).

Methods: Parallel saturation and inhibition studies were performed using well-characterised radioligand binding assays and a Brandel Cell Harvester.

Results: MgCl2 produced a concentration-dependent decrease (44%), whereas Gpp(NH)p increased [3H]DPCPX binding (19%).

Functional consequences of perinatal exposure to 3,4-methylenedioxymethamphetamine in rat brain.

1. In this study we have examined methylenedioxymethamphetamine (MDMA)-induced toxicity in perinatal rat brain, related this to normal development of serotonin transporter sites (SERT), and determined whether early exposure to MDMA subsequently alters cerebral function in adults. 2.