astressin-2b and Substance-Withdrawal-Syndrome

Recent studies have provided convincing evidences for co-morbidity between opioid addiction and obsessive-compulsive disorder (OCD), and the involvement of the corticotrophin-releasing factor (CRF) in the effects of morphine-withdrawal. Some scanty evidences also point towards the role of CRF in OCD and related disorders. But, no evidence indicated the role of CRF in morphine withdrawal associated obsessive-compulsive behavior (OCB). Therefore, the present study investigated the role of CRF in morphine-withdrawal induced OCB in mice. Marble-burying behavior in mice was used to assess OCB as this model has good predictive and face validity. The results revealed that acute morphine dose dependently attenuated the marble burying behavior, whereas withdrawal of chronic morphine was associated with significant rise in marble burying behavior. This indicates the differential effect of acute morphine and chronic morphine-withdrawal on OCB. Further, acute treatment with CRF receptor antagonists like antalarmin (2 and 4 μg/mouse, i.c.v.) or astressin-2B (3 and 10 nmol/mouse, i.c.v.) dose dependently attenuated the peak morphine-withdrawal induced increase in marble burying behavior. Moreover, concomitant treatment with antalarmin (4 μg/mouse, i.c.v.) or astressin-2B (10 nmol/mouse, i.c.v.) along with morphine blocked the morphine-withdrawal associated exacerbation of OCB. These results indicate that OCB associated with morphine withdrawal state is partly mediated by the activation of central CRF receptors.

Topics: Animals; Behavior, Animal; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Mice; Morphine; Motor Activity; Narcotics; Obsessive-Compulsive Disorder; Peptide Fragments; Peptides, Cyclic; Pyrimidines; Pyrroles; Receptors, Corticotropin-Releasing Hormone; Substance Withdrawal Syndrome

The neural plasticity mechanisms that underlie learning and memory may also be engaged when drug addiction occurs. It was reported that long-lasting neuroadaptations induced by cocaine use and withdrawal require the participation of hippocampus. However, the role of corticotrophin-releasing factor receptors in this process remains unclear. In the present study, the effects of chronic cocaine treatment (a 14-day cocaine administration, 20 mg/kg i.p., daily) and short-term cocaine withdrawal (a 3-day cocaine extinction following a 14-day cocaine administration) on long-term potentiation (LTP), one prominent cellular mechanism for learning and memory, were assessed in the CA1 region of the rat hippocampal slices. We found that cocaine withdrawal, but not the chronic cocaine administration itself, significantly enhanced the magnitude of LTP in hippocampal slices, as compared with that in saline controls. Selective blockade of corticotrophin-releasing factor receptor subtype 1 (CRF(1)) with the specific antagonist NBI 27914 (100 nM in vitro) attenuated the magnitude of LTP in hippocampal slices from cocaine withdrawal rats, and intriguingly, also from saline control rats, while specific blockade of corticotrophin-releasing factor receptor subtype 2 (CRF(2)) with astressin2-B (100 nM in vitro) selectively attenuated the magnitude of LTP in hippocampal slices from cocaine withdrawal rats. Our data suggest that short-term cocaine withdrawal treatment may cause synaptic plasticity in hippocampus partially via changing the activity of CRF(2) in the hippocampus.

Topics: Analysis of Variance; Aniline Compounds; Animals; Cocaine; Dopamine Uptake Inhibitors; Electric Stimulation; Excitatory Postsynaptic Potentials; Hippocampus; Long-Term Potentiation; Male; Membrane Potentials; Microelectrodes; Neurons; Peptide Fragments; Peptides, Cyclic; Pyrimidines; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Substance Withdrawal Syndrome

We investigated the role of corticotropin-releasing factor type 2 (CRF(2)) receptors in acute, chronic and withdrawal effects of nicotine on feeding behavior in rats. Nicotine was injected intraperitoneally, whereas CRF, CRF(2) receptors agonist urocortin-1 or selective antagonist astressin2-B were administered directly into the hypothalamic paraventricular nucleus (PVN). In acute studies, nicotine, CRF or urocortin-1 produced dose dependent anorexia at 2 and 4h post-injection time-points, however, astressin2-B did not alter the food intake. Prior treatment of CRF or urocortin-1 potentiated the anorectic effect of nicotine, while astressin2-B showed opposite response. Chronic administration of nicotine produced tolerance to anorexia and caused persistent weight loss. However, concomitant treatment with CRF or urocortin-1 resulted in early tolerance to nicotine-induced anorexia. In the same set of animals, while CRF pre-treatment potentiated the weight reducing effect of nicotine, urocortin-1 failed to do so. Although abrupt termination of chronic nicotine treatment caused hyperphagia and weight gain, administration of CRF or urocortin-1 prevented these effects. These results suggest that CRF(2) receptors, within the framework of PVN, may contribute to the acute, chronic and withdrawal responses of nicotine on feeding and body weight.

Topics: Animals; Anorexia; Corticotropin-Releasing Hormone; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Hyperphagia; Injections, Intraperitoneal; Kinetics; Male; Nicotine; Paraventricular Hypothalamic Nucleus; Peptide Fragments; Peptides, Cyclic; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Substance Withdrawal Syndrome; Urocortins; Weight Gain; Weight Loss