title: Mutual independence of 5-HT(2) and α1 noradrenergic receptors in mediating deficits in sensorimotor gating.
abstract: BACKGROUND
  Prepulse inhibition (PPI), a preattentional information-filtering mechanism, is disrupted by serotonin (5-HT) or norepinephrine (NE) agonists to model deficits seen in schizophrenia, but whether this effect occurs through interactions between these systems is not known.
  
  
  OBJECTIVE
  These studies investigated whether PPI/activity changes induced by agonists of one system were dependent on neurotransmission within the other.
  
  
  METHODS
  Male Sprague-Dawley rats received the 5-HT(2) receptor agonist DOI (1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane) (0, 0.3 mg/kg), with or without antagonists for α1 (prazosin:0, 0.3, or 1 mg/kg) or β (timolol:0, 3, or 10 mg/kg) receptors or their combination (0 or 0.3 mg/kg prazosin + 3 mg/kg timolol), or the 5-HT(2) antagonist ritanserin (0, 2 mg/kg). Separately, the α1-adrenergic receptor agonist cirazoline (0, 0.68 mg/kg) was given with and without ritanserin (0, 0.5, or 2 mg/kg) or the NE antagonists (0 or 0.3 mg/kg prazosin + 3 mg/kg timolol). Finally, combinations of subthreshold doses of DOI (0, 0.01, 0.025 mg/kg) and cirazoline (0, 0.1, 0.25 mg/kg) were tested for their ability to disrupt PPI, and concomitant administration of all three antagonists (0 vs. 0.3 mg/kg prazosin + 3 mg/kg timolol + 2 mg/kg ritanserin) was assessed for its ability to modify PPI. Locomotion was assessed in an additional set of experiments.
  
  
  RESULTS
  Doses/combinations of prazosin and timolol that reversed cirazoline-induced effects did not alter DOI-induced effects, and ritanserin did not affect cirazoline at doses that blocked DOI-mediated effects. Concomitant antagonism of α1 + β + 5-HT(2) receptors did not modify PPI, nor did combinations of subthreshold doses of cirazoline and DOI.
  
  
  CONCLUSIONS
  5-HT(2) receptors and α1 and β NE receptors may act through independent mechanisms to modulate sensorimotor gating and locomotor activity.
authors.affiliation: Department of Psychiatry, UW-Madison, Madison, WI, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Baisley
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Fallace
authors.forename: Abha K
authors.initials: AK
authors.lastname: Rajbhandari
authors.forename: Vaishali P
authors.initials: VP
authors.lastname: Bakshi
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000503:physiopathology; D055139:Sensory Gating / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists