Philip V. Holmes

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Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB(1) receptors in the periaqueductal(More)
Enkephalins are endogenous opioid peptides that are derived from a pre-proenkephalin precursor protein. They are thought to be vital in regulating many physiological functions, including pain perception and analgesia, responses to stress, aggression and dominance. Here we have used a genetic approach to study the role of the mammalian opioid system. We(More)
This review aims to stimulate new ways of thinking about how to model depression in rats and mice. The article is founded on the premise that anthropomorphic inferences should be removed entirely from research involving rodents. The application of animal models to study depression over the past 30 years has been based largely on nonempirical and hence(More)
The antialcoholism medication disulfiram (Antabuse) inhibits aldehyde dehydrogenase (ALDH), which results in the accumulation of acetaldehyde upon ethanol ingestion and produces the aversive ‘Antabuse reaction’ that deters alcohol consumption. Disulfiram has also been shown to deter cocaine use, even in the absence of an interaction with alcohol, indicating(More)
The effects of neuropeptide-Y were examined in the forced swim model of depression in rats. Following a 15-min preswim, four groups of rats were given three intracerebroventricular (i.c.v.) injections of neuropeptide-Y (0.5, 5, or 10 microg) or saline over a 24-h period. Several behaviors were subsequently measured during a 5-min forced swim. Neuropeptide-Y(More)
Affective disorders and substance abuse frequently coexist, yet few previous studies have examined drug self-administration using animal models of depression. The olfactory-bulbectomized rat is a well-established model that exhibits a high degree of neurochemical similarity to depression. Olfactory bulbectomy (OBX) increases dopamine receptor densities in(More)
A sexual dimorphism in stress-induced alterations in renal peripheral benzodiazepine receptors (PBR) was recently reported. The present paper includes five experiments examining the etiology of this sex difference. Surgical removal of ovaries and testes was ineffective in altering the renal PBR stress response in both male and female rats. A diurnal(More)
Studies in both humans and rodents suggest that exercise can be neuroprotective, but the mechanisms by which this occurs are still poorly understood. Three weeks of voluntary, physical activity in rats upregulates prepro-galanin messenger RNA levels in the locus coeruleus. Galanin is a neuropeptide extensively coexisting with norepinephrine that decreases(More)
Previous experiments have reported increased seizure susceptibility in transgenic mice lacking normal neuropeptide-Y (NPY) gene expression (i.e. NPY 'knock-out' mice). A critical issue inherent in such experiments concerns the confounding of developmental influences of NPY and its neurotransmitter functions in the mature organism. The present experiments(More)
The aim of the present studies was to determine the extent to which changes in defensive behaviors could account for some of the behavioral effects of bilateral olfactory bulbectomy (OBX) in rats. Four tests of aversively-motivated behavior were conducted in bulbectomized and sham-operated rats: activity in a dimly lit or brightly lit open field, passive(More)