Dissociable effects of dopamine D1 and D2 receptors on compulsive ingestion and pivoting movements elicited by disinhibiting the ventral pallidum.

Previous studies have shown that infusion of a GABA receptor antagonist, such as bicuculline (bic), into the ventral (pallidum VP) of rats elicits vigorous ingestion in sated subjects and abnormal pivoting movements. Here, we assessed if the ingestive effects generalize to the lateral preoptic area (LPO) and tested both effects for modulation by dopamine receptor signaling. Groups of rats received injections of the dopamine D2 receptor antagonist, haloperidol (hal), the D1 antagonist, SCH-23390 (SCH), or vehicle (veh) followed by infusions of bic or veh into the VP or LPO.

The lateral preoptic area and ventral pallidum embolden behavior.

While recently completing a study of the effects of stimulating the lateral preoptic area (LPO) and ventral pallidum (VP) on locomotion and other movements, we also noticed LPO and VP effects on motivational drive and threat tolerance. Here, we have investigated these latter effects by testing conditioned place preference (CPP), behavior on the elevated plus maze (EPM) and the willingness of sated rats to occupy a harshly lit open field center to acquire sweet pellets, a measure of threat tolerance, following infusions of vehicle or bicuculline (bic) into the LPO and VP. LPO-bic infusions robustly increased total locomotion, and, in direct proportion, occupancy of both the harshly lit field center and open arms of the EPM.

Lateral preoptic and ventral pallidal roles in locomotion and other movements.

The lateral preoptic area (LPO) and ventral pallidum (VP) are structurally and functionally distinct territories in the subcommissural basal forebrain. It was recently shown that unilateral infusion of the GABA receptor antagonist, bicuculline, into the LPO strongly invigorates exploratory locomotion, whereas bicuculline infused unilaterally into the VP has a negligible locomotor effect, but when infused bilaterally, produces vigorous, abnormal pivoting and gnawing movements and compulsive ingestion. This study was done to further characterize these responses.

Abundant collateralization of temporal lobe projections to the accumbens, bed nucleus of stria terminalis, central amygdala and lateral septum.

Behavioral flexibility is subserved in part by outputs from the cerebral cortex to telencephalic subcortical structures. In our earlier evaluation of the organization of the cortical-subcortical output system (Reynolds and Zahm, J Neurosci 25:11757-11767, 2005), retrograde double-labeling was evaluated in the prefrontal cortex following tracer injections into pairs of the following subcortical telencephalic structures: caudate-putamen, core and shell of the accumbens (Acb), bed nucleus of stria terminalis (BST) and central nucleus of the amygdala (CeA). The present study was done to assess patterns of retrograde labeling in the temporal lobe after similar paired tracer injections into most of the same telencephalic structures plus the lateral septum (LS).

Protracted maturation of forebrain afferent connections of the ventral tegmental area in the rat.

The mesocorticolimbic dopamine system has long attracted the interest of researchers concerned with the unique gamut of behavioral and mental health vulnerabilities associated with adolescence. Accordingly, the development of the mesocorticolimbic system has been studied extensively, but almost exclusively with regard to dopaminergic output, particularly in the nucleus accumbens and medial prefrontal cortex. To the contrary, the ontogeny of inputs to the ventral tegmental area (VTA), the source of mesocorticolimbic dopamine, has been neglected.

Oxidative stress disruption of receptor-mediated calcium signaling mechanisms.

Background: Oxidative stress increases the cytosolic content of calcium in the cytoplasm through a combination of effects on calcium pumps, exchangers, channels and binding proteins. In this study, oxidative stress was produced by exposure to tert-butyl hydroperoxide (tBHP); cell viability was assessed using a dye reduction assay; receptor binding was characterized using [3H]N-methylscopolamine ([3H]MS); and cytosolic and luminal endoplasmic reticulum (ER) calcium concentrations ([Ca2+]i and [Ca2+]L, respectively) were measured by fluorescent imaging.

Results: Activation of M3 muscarinic receptors induced a biphasic increase in [Ca2+]i: an initial, inositol trisphosphate (IP3)-mediated release of Ca2+ from endoplasmic reticulum (ER) stores followed by a sustained phase of Ca2+ entry (i.

Honokiol blocks store operated calcium entry in CHO cells expressing the M3 muscarinic receptor: honokiol and muscarinic signaling.

Background: Honokiol, a cell-permeable phenolic compound derived from the bark of magnolia trees and present in Asian herbal teas, has a unique array of pharmacological actions, including the inhibition of multiple autonomic responses. We determined the effects of honokiol on calcium signaling underlying transmission mediated by human M3 muscarinic receptors expressed in Chinese hamster ovary (CHO) cells. Receptor binding was determined in radiolabelled ligand binding assays; changes in intracellular calcium concentrations were determined using a fura-2 ratiometric imaging protocol; cytotoxicity was determined using a dye reduction assay.