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Effect of gabapentin on cognitive processes in rats not exposed and exposed to tobacco smoke during fetal life

Department of Pharmacoeconomics and Social Pharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland

E Nowakowska

Department of Pharmacoeconomics and Social Pharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland elapharm{at}amp.edu.pl

K Kus

Department of Pharmacoeconomics and Social Pharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland

C Sadowski

Department of Toxicology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland

A Matschay

Department of Pharmacoeconomics and Social Pharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland

Cognitive deficits, including memory deficiencies, are currently deemed one of key symptoms of psychopathologic mental disorders or epilepsy. The impairment of neurocognitive processes could be due to the administered therapy, in particular combined therapy or therapy using antiepileptics of older type. Gabapentin (GBP) is one of new antiepileptics with normothymic properties. It is known that epileptic patients run a significant risk of developing depression and mood changes. Smoking may also have a negative effect on memory processes and efficacy of administered drugs. Note that smoking in pregnant women also leads to neurobehavioral changes in their children. The objective of our research was to evaluate the effect of GBP on memory functions and antidepressant effect in rats not exposed and exposed to tobacco smoke in fetal life. We were also intent on finding whether GBP has an anticonvulsant effect in contact and without contact with tobacco smoke, and whether it affects motor coordination in animals if administered in the dose of 25 mg/kg. Spatial memory of the animals was assessed in the Morris test and the antidepressant effect in the Porsolt test. The ED₅₀ value was determined in the Swinyard maximum electric shock test, and the effect on motor coordination was assessed in the chimney test. GBP administered in the dose of 25 mg/kg intraperitoneal (i.p.) significantly reduced the immobility time on days 1 and 7 of the test in animals exposed to tobacco smoke, and on days 7 and 14 of the test in rats not exposed to tobacco smoke. Upon single and multiple administration of GBP to animals not exposed to tobacco smoke, the spatial memory improved, whereas in animals exposed to tobacco smoke in fetal life tolerance for procognitive effect was observed on day 21 of the test. It has been found that in rats not exposed to tobacco smoke, ED₅₀ of GBP was 28.73 mg/kg, whereas in animals exposed to tobacco smoke in fetal life, ED₅₀ was 46.2 mg/kg. Upon 14 and 21 days of drug administration, motor coordination was impaired in both GBP receiving animal groups. In conclusion, GBP beside its anticonvulsant efficacy also improves memory processes and has antidepressant effect. We also proved that GBP may reverse cognitive deficits concerning working memory induced by prenatal exposure to tobacco smoke and may have antidepressant effect in rats exposed to tobacco smoke.

Key Words: antidepressant effect • antiepileptic effect • gabapentin • prenatal • rats • working memory

Human & Experimental Toxicology, Vol. 27, No. 12, 883-894 (2008)
DOI: 10.1177/0960327108098334


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