Role of dopamine in dorsal medial prefrontal cortex in yohimbine-induced reinstatement of food seeking in rats

In humans, relapse to maladaptive eating habits during dieting is often provoked by stress.Weadapted a drug relapse-reinstatement model to study the role of stress in relapse to food seeking (Nair et al., Prog. Neurobiol., 2009). In our model, the anxiogenic drug yohimbine, an alpha-2 adrenoceptor antagonist, that causes stress-like responses in humans and laboratory animals, reliably reinstates food seeking.Werecently found that yohimbine-induced reinstatement of food seeking is attenuated by systemic injections of SCH23390 (a D1-family receptor antagonist) but not clonidine (an alpha-2 adrenoceptor agonist). Here, we studied the role of the medial prefrontal cortex (mPFC) in yohimbine-induced reinstatement. We trained food-restricted rats to lever-press for 35% high-fat pellets every other day (9–15 3 h sessions). We then extinguished the food-reinforced operant responding for 10–14 days by removing the pellets. Subsequently, we tested the effect of systemic injections of yohimbine (0, 2 mg/kg) on reinstatement of food seeking. In Exp. 1we found that yohimbine-induced reinstatement was associated with strong induction of Fos (a marker of neuronal activity) in the dorsal mPFC and weaker Fos induction in the ventral mPFC. In Exp. 2 we found that dorsal but not ventral mPFC injections of the D1-family receptor antagonist SCH23390 (0.5, 1.0g/side) decreased yohimbine-induced reinstatement of food seeking. Our data indicate a critical role of dorsal mPFC dopamine in reinstatement food seeking induced by the pharmacological stressor yohimbine

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine

Simple bone cyst presenting as an incidental finding in pretreatment orthodontic radiograph: A case report

Pretreatment radiographs, especially panoramic and lateral cephalometric are routinely used as an aid in orthodontic diagnosis and treatment planning. Sometimes abnormalities may be detected as incidental findings in such radiographs that require medical or odontological management. Simple bone cyst is an uncommon lesion mostly occurring in young individuals; it is often asymptomatic and accidently discovered during routine radiological examination. Mostly the pathology presents as a unilocular radiolucency in the mandible between canine and third molar. A definite diagnosis is invariably achieved during surgery as it presents as an empty cavity without lining. We present a case of a simple bone cyst of the body of mandible identified during routine pretreatment orthodontic radiograph

Role of Dorsal Medial Prefrontal Cortex Dopamine D1-Family Receptors in Relapse to High-Fat Food Seeking Induced by the Anxiogenic Drug Yohimbine

In humans, relapse to maladaptive eating habits during dieting is often provoked by stress. In rats, the anxiogenic drug yohimbine, which causes stress-like responses in both humans and nonhumans, reinstates food seeking in a relapse model. In this study, we examined the role of medial prefrontal cortex (mPFC) dopamine D1-family receptors, previously implicated in stress-induced reinstatement of drug seeking, in yohimbine-induced reinstatement of food seeking. We trained food-restricted rats to lever press for 35% high-fat pellets every other day (9–15 sessions, 3 h each); pellet delivery was accompanied by a discrete tone-light cue. We then extinguished operant responding for 10–16 days by removing the pellets. Subsequently, we examined the effect of yohimbine (2 mg/kg, i.p.) on reinstatement of food seeking and Fos (a neuronal activity marker) induction in mPFC. We then examined the effect of systemic injections of the D1-family receptor antagonist SCH23390 (10 μg/kg, s.c.) on yohimbine-induced reinstatement and Fos induction, and that of mPFC SCH23390 (0.5 and 1.0 μg/side) injections on this reinstatement. Yohimbine-induced reinstatement was associated with strong Fos induction in the dorsal mPFC and with weaker Fos induction in the ventral mPFC. Systemic SCH23390 injections blocked both yohimbine-induced reinstatement and mPFC Fos induction. Dorsal, but not ventral, mPFC injections of SCH23390 decreased yohimbine-induced reinstatement of food seeking. In addition, dorsal mPFC SCH23390 injections decreased pellet-priming-induced reinstatement, but had no effect on ongoing high-fat pellet self-administration or discrete-cue-induced reinstatement. Results indicate a critical role of dorsal mPFC dopamine D1-family receptors in stress-induced relapse to palatable food seeking, as well as relapse induced by acute re-exposure to food taste, texture, and smell