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To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS(More)
The 5-HT2C receptor is one of three closely related receptor subtypes in the 5-HT2 receptor family. 5-HT2A and 5-HT2B selective antagonists have been described. However, no 5-HT2C selective antagonists have yet been disclosed. As part of an effort to further explore the function of 5-HT2C receptors, we have developed a selective 5-HT2C receptor antagonist,(More)
In the present studies we investigated the actions of ondansetron, a prototypic 5-hydroxytryptamine3 (5-HT3) receptor antagonist, on performance in a complex spatial navigation/memory task in rats. Specifically, we compared the activity of ondansetron to that of the cholinesterase inhibitor physostigmine in attenuating two distinct cognitive deficits in the(More)
The actions of linopirdine (DuP 996; 3,3-bis[4-pyrindinylmethyl]-1-phenylindolin-2-one) were evaluated in rats and mice in several cognitive behavioral tests, and for its effects on hippocampal acetylcholine (ACh) overflow in rats. Using mice treated with the muscarinic receptor antagonist, scopolamine, we studied the effects of linopirdine on retention of(More)
In the present studies we investigated the actions of (R)- and (S)-zacopride, potent 5-HT3 receptor antagonists with 5-HT4 receptor agonists properties, on performance in a spatial learning and memory task in rats, the Morris water maze. A significant cognitive/performance deficit, as indicated by the increased escape latency across several trials, was(More)
The novel anti-epileptic drugs lamotrigine, felbamate and gabapentin were compared in rat experimental models of acute (tail flick) and chronic pain: the chronic constriction injury and spinal nerve ligation models. Lamotrigine (10-100 mg/kg, s.c.), felbamate (150-600 mg/kg, i.p.) and gabapentin (30-300 mg/kg, i.p.) each reversed cold allodynia (chronic(More)
Activation of central 5-hydroxytryptamine (5-HT4) receptors may enhance cognitive performance. In the present study, the effects of two novel, potent and selective 5-HT4 receptor agonists, RS 67333 (1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-burtl-4-piperidinyl)- 1-propanone) and RS 67506 (1-(4-amino-(More)
Recent evidence indicates that the 5-HT4 subtype of serotonin receptor may modulate central cholinergic activity in regions of the mammalian CNS important to memory such as the frontal cortex, hippocampus and amygdala. These receptors could represent targets for drugs designed for the symptomatic therapy of Alzheimer's disease (AD) and other disorders of(More)
The present studies examined the effects of acute cocaine administration, chronic cocaine administration and cocaine withdrawal on behavior in the Conditioned Suppression of Drinking (CSD) conflict paradigm, an animal model for the study of anxiety. In daily 10-minute sessions, water deprived rats were trained to drink from a tube that was occasionally(More)
We tested cholinergic agents in delayed matching and nonmatching to position. Each task had a delay between the presentation of information and the chance to act on it later. We used a titrating procedure, new to experiments with rats, to determine the delay. Linopirdine (0.1 mg/kg), which releases acetylcholine, and physostigmine (0.1 mg/kg), a(More)