Effects of nicotine on quinpirole- and dizocilpine (MK-801)-induced sensorimotor gating impairments in rats.
BACKGROUND
Prepulse inhibition (PPI) of the acoustic startle response (ASR) is used as an index of sensorimotor gating to assess preattentive processes. Impairments in PPI have been observed in many neuropsychiatric disorders, especially schizophrenia. Administration of the glutamate N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) or dopamine receptor (D2/D3) agonist quinpirole (QNP) results in impairment (reduction) of PPI in rats. Nicotine, on the other hand, may have beneficial effects on attentional/cognitive functions.


OBJECTIVE
The purpose of the current set of experiments was to investigate the effects of acute and chronic nicotine on MK-801- and QNP-induced PPI impairments.


METHODS
Adult female Sprague-Dawley rats were treated acutely or chronically by various doses of nicotine alone or followed by an acute dose of MK-801 (0.15 mg/kg) or QNP (0.5 mg/kg). All drugs were administered intraperitoneally. Controls received saline in lieu of any drug, and ASR and PPI in each animal was evaluated 10 min after the last injection.


RESULTS
Both MK-801 and QNP consistently impaired PPI. Administration of nicotine acutely (0.05-0.4 mg/kg) or chronically (0.2 or 0.4 mg/kg daily for 1 week) did not have any effect of its own on ASR or PPI or on MK-801-induced PPI impairment. Acute administration of 0.2 mg/kg nicotine did not have any effect on QNP-induced reduction in PPI, whereas the higher dose of 0.4 mg/kg significantly attenuated this impairment. Chronic daily administration of either 0.2 or 0.4 mg/kg nicotine for 1 week nearly normalized the QNP-induced impairments in PPI.


CONCLUSIONS
The effect of nicotine on sensorimotor gating is dependent on the procedure as well as the dose of nicotine and appears to be efficacious against dopaminergic rather than glutamatergic disruption of PPI in rats.
Nespor
Amy A
AA
Department of Pharmacology, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, USA.
Tizabi
Yousef
Y
D000161:Acoustic Stimulation; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D009538:Nicotine / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000819:agonists; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013216:Reflex, Startle / Q000187:drug effects*; D055139:Sensory Gating / Q000187:drug effects*; D014029:Tobacco Use Disorder / Q000503:physiopathology
D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D016194:Receptors, N-Methyl-D-Aspartate; D019257:Quinpirole; D016291:Dizocilpine Maleate; D009538:Nicotine; D004298:Dopamine