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Long postmenopausal lifespans distinguish humans from all other primates. This pattern may have evolved with mother-child food sharing, a practice that allowed aging females to enhance their daughters' fertility, thereby increasing selection against senescence. Combined with Charnov's dimensionless assembly rules for mammalian life histories, this(More)
Reproductive experiences for women in today's affluent Western nations differ from those of women in hunting and gathering societies, who continue the ancestral human pattern. These differences parallel commonly accepted reproductive risk factors for cancers of the breast, endometrium and ovary. Nutritional practices, exercise requirements, and body(More)
RATIONALE Ketamine induces, in both humans and rodents, behaviours analogous to some of the symptoms of schizophrenia. OBJECTIVES To utilise pharmacological magnetic resonance imaging (phMRI) techniques that identify changes in blood-oxygenation-level-dependent (BOLD) contrast to determine the temporal and spatial neuronal activation profile of ketamine(More)
Acid-sensing ion channels (ASICs) are a class of ion channels activated by extracellular protons and are believed to mediate the pain caused by tissue acidosis. Although ASICs have been widely studied, little is known about their regulation by inflammatory mediators. Here, we provide evidence that nitric oxide (NO) potentiates the activity of ASICs.(More)
Human monogenic pain syndromes have provided important insights into the molecular mechanisms that underlie normal and pathological pain states. We describe an autosomal-dominant familial episodic pain syndrome characterized by episodes of debilitating upper body pain, triggered by fasting and physical stress. Linkage and haplotype analysis mapped this(More)
Most neuronal models of learning assume that changes in synaptic strength are the main mechanism underlying long-term memory (LTM) formation. However, we show here that a persistent depolarization of membrane potential, a type of cellular change that increases neuronal responsiveness, contributes significantly to a long-lasting associative memory trace. The(More)
Despite the discovery of ion channels that are activated by protons, we still know relatively little about the signaling of acid pain. We used a novel technique, iontophoresis of protons, to investigate acid-induced pain in human volunteers. We found that transdermal iontophoresis of protons consistently caused moderate pain that was dose-dependent. A(More)
Acute noxious stimuli activate a specialized neuronal detection system that generates sensations of pain and, generally, adaptive behavioral responses. More persistent noxious stimuli notably those associated with some chronic injuries and disease states not only activate the pain-signaling system but also dramatically alter its properties so that weak(More)
Pre-clinical models of anxiety, particularly the elevated plus-maze (EPM), have been shown to be sensitive to a variety of methodological variations. Recent research has implicated circadian phase of testing in influencing the behavioural profile of 5-HT(1A) ligands on the EPM. The present study investigated the effects of testing animals during the dark(More)
RATIONALE AND OBJECTIVES m-Chlorophenylpiperazine (mCPP) induces panic in humans and dose dependently increases unconditioned escape behaviour in a novel pre-clinical model of extreme anxiety in rats, the unstable elevated exposed plus maze (UEEPM). Numerous studies indicate that the anxiogenic effects of mCPP may be mediated by its action at the 5-HT2C(More)