Effect of chronic treatment with piracetam and tacrine on some changes caused by thymectomy in the rat brain.

Thymectomized rats, 5 weeks after surgery, showed a significant impairment in learning and memory as shown by deficits in passive avoidance and in the Morris water maze test. The behaviour of the thymectomized rats in the "open field" apparatus was largely unchanged. Following treatment for 20 days with either piracetam (500 mg/kg) or tacrine (3.0 mg/kg), the deficit in passive avoidance learning was largely reversed. Chronic treatment with tacrine also reversed the deficit in the behaviour of the thymectomized rats in the Morris water maze. The effects of thymectomy on the biogenic amines and some of their metabolites in the amygdaloid cortex, hypothalamus, striatum and olfactory bulbs were also determined. Relative to the sham-operated controls, thymectomy resulted in a reduction in the noradrenaline concentration in the amygdala, hypothalamus, and olfactory bulbs. This effect was reversed by chronic piracetam and tacrine treatments. The concentration of dopamine was also reduced in the olfactory bulbs after thymectomy whereas in the striatum the concentration of 5-hydroxytryptamine (5-HT; serotonin) was increased. The concentration of gamma amino butyric acid (GABA) was determined in amygdaloid cortex and hippocampus only. The only significant change occurred following chronic treatment of thymectomized rats with tacrine, when a significant elevation of GABA was found. Neither piracetam nor tacrine produced any change in the amines of their metabolites in the sham-operated controls. Tacrine, however, elevated the dopamine and reduced the 5-HT content of the hypothalamus and increased the 3,4-dihydroxylphenylacetic acid concentration of the striatum of thymectomized rats. Examination of the differential white blood cell count of the thymectomized rats showed that the percentage of lymphocytes was decreased, and the percentage of neutrophils increased, relative to the sham-operated controls. Chronic lacrine, but not piracetam, treatment reversed the lesion-induced changes.