title: H3 receptor blockade by thioperamide enhances cognition in rats without inducing locomotor sensitization.
abstract: BACKGROUND
  Attention deficit hyperactivity disorder (ADHD) is currently treated with psychomotor stimulants, including methylphenidate and amphetamine. Several adverse effects are associated with these drugs, however, such as agitation and abuse. H(3) receptor antagonists are under clinical investigation for ADHD.
  
  
  OBJECTIVE
  To investigate the potential of thioperamide, a prototypical H(3) receptor antagonist, to enhance learning and attention while inducing no effects on locomotor stimulation and sensitization, or alterations in ACTH levels.
  
  
  METHODS
  Thioperamide (1, 3, 10, 30 mg/kg) was administered prior to testing in a multi-trial, inhibitory avoidance response in rat pups (five trials separated by 1 min) to evaluate attention/cognition. Locomotor sensitization and cross-sensitization was assessed following administration of methylphenidate (3 mg/kg), cocaine (10 mg/kg), or thioperamide (1, 3, 10 mg/kg).
  
  
  RESULTS
  Thioperamide significantly enhanced performance of the five-trial inhibitory avoidance response with efficacy similar to that previously reported for methylphenidate. Administration of amphetamine, methylphenidate and cocaine produced significant locomotor sensitization, however. In contrast, thioperamide did not induce locomotor stimulation or sensitization, nor did it cross-sensitize to the stimulant effects of amphetamine or cocaine. The repeated administration of methylphenidate significantly elevated ACTH levels, while thioperamide did not affect this neuroendocrine endpoint.
  
  
  CONCLUSIONS
  H(3) receptor blockade may offer a safer alternative to psychomotor stimulants for the treatment of ADHD.
authors.affiliation: Neuroscience Research, Abbott Laboratories, AP9A, D4N5, Abbott Park, IL 60064, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Komater
authors.forename: Kaitlin E
authors.initials: KE
authors.lastname: Browman
authors.forename: Peter
authors.initials: P
authors.lastname: Curzon
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Hancock
authors.forename: Michael W
authors.initials: MW
authors.lastname: Decker
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Fox
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001288:Attention / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D003913:Dextroamphetamine / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D018100:Receptors, Histamine H3 / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D006633:Histamine Antagonists; D010880:Piperidines; D018100:Receptors, Histamine H3; D008774:Methylphenidate; D000324:Adrenocorticotropic Hormone; D003042:Cocaine; C052075:thioperamide; D003913:Dextroamphetamine