Abstract
Rationale
The α7 subtype of the nicotinic receptor plays an important role in auditory sensory gating. Schizophrenics show deficient sensory gating and abnormalities in the number and regulation of nicotinic receptors. Prepulse inhibition (PPI) deficits exhibited by isolation-reared rats are thought to model the sensorimotor gating deficits seen in schizophrenia.
Objective
To examine the role of nicotinic α7 receptors in the isolation-rearing rat model, we tested whether the selective α7 receptor agonist (R)-N-(1-Azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide) (compound A) could reverse isolation-rearing-induced PPI deficits, and investigated α7 receptor RNA expression in the hippocampus, prefrontal cortex, cerebellum, nucleus accumbens and thalamus, and α7 receptor protein expression in the hippocampus of isolation- and group-reared rats.
Method
Rats reared in isolation or groups of five from weaning were tested in the PPI paradigm under conditions of variable inter-stimulus interval (ISI) (pulse=110 dB/50 ms; prepulse=75 dB/30 ms; ISI=30, 100 and 300 ms) 30 min following administration of compound A (3.2–10 mg/kg i.p.). α7 Receptor expression was measured by TaqMan RT-PCR (total RNA) and autoradiography (protein).
Results
Isolation-rearing-induced PPI deficits were attenuated by both doses of compound A at 100-ms ISI and by 10 mg/kg at 300-ms ISI. Expression of α7 receptor RNA and protein was unaltered in isolation-reared rats.
Conclusion
Although altered α7 receptor expression may not underlie the phenotype of isolation-reared rats, the activation of these receptors may be of benefit in re-establishing efficient gating function.
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Cilia, J., Cluderay, J.E., Robbins, M.J. et al. Reversal of isolation-rearing-induced PPI deficits by an α7 nicotinic receptor agonist. Psychopharmacology 182, 214–219 (2005). https://doi.org/10.1007/s00213-005-0069-5
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DOI: https://doi.org/10.1007/s00213-005-0069-5