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The interoceptive stimulus induced by clozapine (5 mg/kg, i.p.) has been characterized in an operant drug discrimination procedure in the rat using a wide range of receptor subtype-selective agonists and antagonists. Only the muscarinic receptor antagonist scopolamine generalized fully to clozapine (>80%). Partial generalization (defined here as 40% maximal(More)
Drug discrimination methodology has been used in a number of ways to analyze the actions of novel and putative novel antipsychotics in vivo. Recent studies suggest (a) in contrast to earlier theorizing, antagonism of the low-dose d-amphetamine stimulus in rats may not be an effective screen for novel antipsychotics; (b) dopamine D2-like agonists and(More)
RATIONALE In schizophrenics, clozapine has been reported to induce various withdrawal signs and rapid onset relapse to psychosis on cessation of chronic treatment. OBJECTIVE The study was designed to develop an animal model of one aspect of clozapine tolerance and withdrawal using core body temperature measures. METHODS Two groups of 15 female Wistar(More)
Novel antipsychotic drugs (APDs) have enhanced therapeutic actions compared to 'typical' APDs. However, clinical studies indicate that some induce marked weight gain. We attempted to model this effect in female Wistar rats given olanzapine chronically at 4 mg/kg b.i.d (4.5 h between injections). Such rats showed marked weight gain, which was statistically(More)
Two groups of female Wistar rats were trained to discriminate two doses (0.075 and 0.0375 mg/kg) of the noncompetitive NMDA antagonist MK-801 (dizocilpine) in a food-rewarded operant FR30 drug discrimination task. The atypical neuroleptic clozapine (2-6 mg/kg) produced only minimal antagonism (max. 32%) of the MK-801 cue at either training dose, and the(More)
Dopamine D3 receptors have been implicated in the aetiology of schizophrenia and the actions of antipsychotic drugs. The initial studies reported here assessed the involvement of such receptors in the in vivo actions of the atypical antipsychotic clozapine and the putative D3-preferring antagonist PNU-99194A in drug discrimination assays. Rats trained to(More)
BACKGROUND Members of the M2 family of peptidases, related to mammalian angiotensin converting enzyme (ACE), play important roles in regulating a number of physiological processes. As more invertebrate genomes are sequenced, there is increasing evidence of a variety of M2 peptidase genes, even within a single species. The function of these ACE-like proteins(More)
BACKGROUND Curcumin is a food chemical present in tumeric (Curcuma longa) that has pharmacological activity to suppress carcinogenesis and inhibits multiple signaling pathways such as nuclear factor kappaB (NF-kappaB), cyclooxygenase-2 (Cox-2) and interleukin-8 (IL-8). Oral curcumin has poor oral bioavailability limiting its clinical activity; however, a(More)
The effects of partially purified insulin-generated mediators from rat skeletal muscle were compared to those of insulin on intact adipocytes. Insulin and insulin mediator stimulated both pyruvate dehydrogenase and glycogen synthase activity of intact adipocytes. In contrast, insulin stimulated glucose oxidation and 3-O-methylglucose transport, whereas(More)
Recent studies indicate that the midcycle gonadotropin surge in the human occurs without an increase in hypothalamic gonadotropin-releasing hormone (GnRH) pulse frequency. In addition, previous studies employing a GnRH antagonist to provide a semiquantitative estimate of endogenous GnRH secretion suggest that the overall amount of GnRH secreted is decreased(More)