NICOTINE TREATMENT COUNTERACTS PERINATAL ASPHYXIA-INDUCED CHANGES IN THE MESOSTRIATAL LIMBIC DOPAMINE SYSTEMS AND IN MOTOR BEHAVIOR IN THE 4-WEEK-OLD MALE-RAT

In the present study, the effects of nicotine treatment on the changes induced by perinatal asphyxia in exploratory and D-amphetamine-induce d behaviour, and in the number of brain tyrosine hydroxylase-immunorea ctive nerve cell bodies were investigated in four-week-old male rats. Asphyxia was induced in pups by placing the fetuses, still in their ut erus horns removed by hysterectomy from full-term pregnant rats, in a 37 degrees C water bath for 15-16 min or 19-20 min. Surviving male pup s were treated with nicotine via suckling from surrogate mothers impla nted subcutaneously with Alzet minipumps containing nicotine (0.2 mu m ol/kg per h) for four weeks. The minipumps implanted in the mothers of sham-treated animals contained saline only. After treatment, explorat ory behaviour and D-amphetamine-induced behaviour was analysed in a co mputerized ''activity'' box. After the behavioural experiments, the ra ts were taken for tyrosine hydroxylase immunohistochemistry, and the t otal number of tyrosine hydroxylase immunoreactive cell bodies were co unted in the A9 and A10 regions of the substantia nigra and the ventra l tegmental area, respectively. Nicotine serum levels were measured us ing gas chromatography in selected asphyctic and control pups at diffe rent periods after delivery. During the exploratory phase, in saline-n urtured rats, 15-16 min of asphyxia slightly increased (approximate to 25%) locomotion, motility and rearing. In contrast, 19-20 min of asph yxia reduced the locomotion and rearing by approximate to 50%, as comp ared to controls. An increase in amphetamine-induced behaviours was ob served after 15-16 min, but not after 19-20 min of asphyxia, as compar ed to controls. At the histochemical level, saline-nurtured 19-20 min, but not 15-16 min asphyctic rats showed a significant increase (appro ximate to 30%) in the number of tyrosine hydroxylase immunoreactive ce ll bodies in both A9 and A10 regions. The average of nicotine serum le vels detected in pups nurtured for a four week period by nicotine-trea ted mothers was approximate to 5 ng/ml. The nicotine treatment did not significantly change the pattern of behaviour elicited by a new envir onment or by D-amphetamine in caesarean-delivered controls. However, n icotine counteracted the asphyxia-induced behavioural changes observed in the 19-20 min asphyctic group. Immunohistochemical analysis reveal ed that the nicotine treatment also counteracted the increase in the n umber of tyrosine hydroxylase immunoreactive neurons in the A9 and A10 regions observed following 19-20 min of perinatal asphyxia. In conclu sion, nicotine treatment counteracted some of the long-term (four week ) behavioural and histochemical consequences of perinatal asphyxia in rats. The possible clinical implications of using nicotine as a treatm ent of asphyxia are discussed.