Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2002-3-7
pubmed:abstractText
Histamine H(3) receptor antagonists have been proposed as potentially useful therapeutic agents for the treatment of several disorders including attention deficit, schizophrenia, depression, and Alzheimer's disease. We have developed a repeated acquisition version of an inhibitory avoidance task using spontaneously hypertensive rat (SHR) pups that we believe provides a reproducible measure of the cognitive and attention deficits often characteristic of these disease states, and evaluated two H(3) receptor antagonists. Male SHR, Wistar (WI) and Wistar Kyoto (WKY) rat pups (20--24 days old) were trained to avoid a mild footshock (0.1 mA, 1 s duration), delivered when the pup had transferred from a brightly lit to a darkened compartment. After the first trial, the pup was removed and returned to its home cage. One minute later, the same pup was replaced in the brightly-lit compartment and the training process repeated. A total of five trials were recorded. SHR pups performed significantly more poorly than WI or WKY pups using this training schedule, and SHR pups were used for all subsequent studies. Methylphenidate and ABT-418, both clinically active in attention deficit hyperactivity disorder (ADHD), were tested to validate the model. Methylphenidate (1 and 3 mg/kg s.c.) and ABT-418 (0.03 mg/kg s.c.) significantly improved SHR pup performance. The H(3) receptor antagonists GT-2331 (1 mg/kg s.c.) and ciproxifan (3 mg/kg s.c.), also significantly, and in a dose-related manner, enhanced performance of the SHR pups. (R)-alpha-methylhistamine (3 mg/kg s.c.) blocked the pro-cognitive effects of ciproxifan, suggesting an H(3) receptor site of action for this compound. This model is useful for evaluating the cognition/attention-enhancing potential of H(3) receptor antagonists.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3-methyl-5-(1-methyl-2-pyrrolidinyl)..., http://linkedlifedata.com/resource/pubmed/chemical/4-(2-(5,5-dimethylhex-1-ynyl)cyclopr..., http://linkedlifedata.com/resource/pubmed/chemical/Anti-Anxiety Agents, http://linkedlifedata.com/resource/pubmed/chemical/Central Nervous System Stimulants, http://linkedlifedata.com/resource/pubmed/chemical/Histamine Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Isoxazoles, http://linkedlifedata.com/resource/pubmed/chemical/Ligands, http://linkedlifedata.com/resource/pubmed/chemical/Methylphenidate, http://linkedlifedata.com/resource/pubmed/chemical/Nicotinic Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Histamine H3, http://linkedlifedata.com/resource/pubmed/chemical/ciproxifan
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0166-4328
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
131
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
151-61
pubmed:dateRevised
2006-3-1
pubmed:meshHeading
pubmed-meshheading:11844582-Animals, pubmed-meshheading:11844582-Anti-Anxiety Agents, pubmed-meshheading:11844582-Arousal, pubmed-meshheading:11844582-Attention Deficit Disorder with Hyperactivity, pubmed-meshheading:11844582-Avoidance Learning, pubmed-meshheading:11844582-Central Nervous System Stimulants, pubmed-meshheading:11844582-Cognition Disorders, pubmed-meshheading:11844582-Disease Models, Animal, pubmed-meshheading:11844582-Histamine Antagonists, pubmed-meshheading:11844582-Imidazoles, pubmed-meshheading:11844582-Impulsive Behavior, pubmed-meshheading:11844582-Isoxazoles, pubmed-meshheading:11844582-Ligands, pubmed-meshheading:11844582-Male, pubmed-meshheading:11844582-Methylphenidate, pubmed-meshheading:11844582-Motor Activity, pubmed-meshheading:11844582-Nicotinic Agonists, pubmed-meshheading:11844582-Psychomotor Performance, pubmed-meshheading:11844582-Pyrrolidines, pubmed-meshheading:11844582-Rats, pubmed-meshheading:11844582-Rats, Inbred SHR, pubmed-meshheading:11844582-Rats, Inbred WKY, pubmed-meshheading:11844582-Receptors, Histamine H3
pubmed:year
2002
pubmed:articleTitle
Effects of histamine H(3) receptor ligands GT-2331 and ciproxifan in a repeated acquisition avoidance response in the spontaneously hypertensive rat pup.
pubmed:affiliation
CNS Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, AP9A D4N5, Abbott Park, IL 60064, USA. gerard.b.fox@abbott.com
pubmed:publicationType
Journal Article