6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) is a novel histamine H 3 receptor antagonist with high affinity for human (pK i ϭ 9.59 -9.90) and rat (pK i ϭ 8.51-9.17) H 3 receptors. GSK189254 is Ͼ10,000-fold selective for human H 3 receptors versus other targets tested, and it exhibited potent functional antagonism (pA 2 ϭ 9.06 versus agonist-induced changes in cAMP) and inverse agonism [pIC 50 Progressive decline in cognitive performance is a key characteristic of Alzheimer's disease (AD) and related dementias, and improving cognitive function in these diseases represents a complex challenge, given the involvement of numerous neurotransmitter systems and brain regions (CoreyBloom, 2002). Current therapies, such as cholinesterase inhibitors, provide only minimal benefit to a subset of patients and for a limited period, so a number of alternative Article, publication date, and citation information can be found at

The 5-hydroxytryptamine(6) (5-ht(6)) was one of the most recent additions to the 5-HT receptor family, selective antagonists have recently been developed and potential functional roles are now becoming apparent. The high affinity of a wide range of psychiatric drugs for the 5-ht(6)receptor, together with its almost exclusive expression in the CNS, being abundant in limbic and cortical regions, has stimulated significant research interest. The 5-ht(6)receptor appears to regulate glutamatergic and cholinergic neuronal activity, and increasing evidence suggests that it may be involved in the regulation of cognition, feeding and, possibly, affective state and seizures. The current article will review all aspects of the discovery, genetics, distribution, pharmacology and function of the 5-ht(6)receptor. Taken together, this wealth of information warrants the use of the upper case nomenclature for the 5-ht(6) receptor to be approved and its true status recognised.

The mGlu2 but not the mGlu3 receptor subtype mediates the actions of the mGluR2/3 agonist, LY379268, in mouse models predictive of antipsychotic activity.

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Rationale: The NMDA receptor antagonist, phencyclidine (PCP), has been shown to induce symptoms characteristic of schizophrenia. A loss in executive function and the ability to shift attention between stimulus dimensions is impaired in schizophrenia; this can be assessed in rodents by the perceptual attentional set-shifting task. Objective: The aim of this study was to investigate whether the deficits induced by sub-chronic PCP in attentional set-shifting could be reversed by sub-chronic administration of clozapine, risperidone or haloperidol. Methods: Adult female hooded-Lister rats received subchronic PCP (2 mg/kg) or vehicle (1 ml/kg) i.p. twice daily for seven days, followed by a seven-day washout period. PCP-treated rats then received clozapine, risperidone, haloperidol or vehicle once daily for seven days and were then tested in the perceptual set-shifting task. Results: PCP significantly (p<0.01) increased the number of trials to reach criterion in the EDS phase when compared to vehicle and this deficit was significantly (p<0.01) attenuated by sub-chronic clozapine (2.5 mg/kg) and risperidone (0.2 mg/kg), but not by sub-chronic haloperidol treatment (0.05 mg/kg). Conclusions:These data show that sub-chronic PCP produced a robust deficit within the EDS phase in the attentional set-shifting task, in female rats. Atypical antipsychotics, clozapine and risperidone, but not the classical agent, haloperidol, significantly improved the PCPinduced cognitive deficit.

Phencyclidine (PCP) produces cognitive deficits of relevance to schizophrenia in animal models. The aim was to investigate the efficacy of the D 1 -like receptor agonist, SKF-38393, to improve PCP-induced deficits in the novel object recognition (NOR) and operant reversal learning (RL) tasks. Rats received either sub-chronic PCP (2 mg/kg) or vehicle for 7 days, followed by a 7-day washout. Rats were either tested in NOR or the RL tasks. In NOR vehicle rats successfully discriminated between novel and familiar objects, an effect abolished in PCP-treated rats. SKF-