TY - JOUR
T1 - Mutual independence of 5-HT 2 and α1 noradrenergic receptors in mediating deficits in sensorimotor gating
AU - Baisley, Sarah K.
AU - Fallace, Katherine L.
AU - Rajbhandari, Abha K.
AU - Bakshi, Vaishali P.
PY - 2012/4
Y1 - 2012/4
N2 - Rationale 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. Objectives 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 cirazo-line 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.
AB - Rationale 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. Objectives 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 cirazo-line 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.
KW - Locomotion
KW - Noradrenergic
KW - Schizophrenia
KW - Serotonergic
KW - Startle
KW - Stereotypy
UR - http://www.scopus.com/inward/record.url?scp=84858446573&partnerID=8YFLogxK
U2 - 10.1007/s00213-011-2490-2
DO - 10.1007/s00213-011-2490-2
M3 - Article
C2 - 21947334
AN - SCOPUS:84858446573
SN - 0033-3158
VL - 220
SP - 465
EP - 479
JO - Psychopharmacology
JF - Psychopharmacology
IS - 3
ER -