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Psychopharmacology (Berl). 2012 Apr;220(3):465-79. doi: 10.1007/s00213-011-2490-2. Epub 2011 Sep 23.

Mutual independence of 5-HT(2) and α1 noradrenergic receptors in mediating deficits in sensorimotor gating.

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1
Department of Psychiatry, UW-Madison, Madison, WI, USA.

Abstract

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 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.

PMID:
21947334
PMCID:
PMC4090044
DOI:
10.1007/s00213-011-2490-2
[Indexed for MEDLINE]
Free PMC Article
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