Postnatal Development of Central Effects of Atropine and Oxotremorine in Dogs in Relation to Brain Development

: The central effects of atropine, methylatropine and oxotremonne have been investigated in dogs at five different ages, i. e. newborn, 3 weeks, 6 weeks, 3 months and adult. The evaluation of the central effects has been made by behavioural and neurological tests, especially designed for the different age groups. In adult dogs 0.5 mg/kg of atropine and 20 mg/kg of methylatropine cause typical behavioural disturbances, i. e. ataxia, non-responsiveness, non-retreating behaviour and increased motor activity, while oxotremorine 0.025 mg/kg produces a pronounced tremor. In the newborn dogs no central effects can be detected with atropine, 0.5-5.0 mg/kg, or methylatropine, 20 mg/kg. Furthermore, tremor can not be elicited with 0.01-1.0 mg/kg of oxotremorine in this age group. Among the 3 weeks old puppies, the neurologically and behaviourally most mature animals show central effects similar to those in the adult following 0.5 mg/kg of atropine, while more immature dogs show no symptoms even after 5.0 mg/kg. The sensitivity to the tremorogenic affect of oxotremorine is the same in this age group as in the adult dogs. At six weeks and three months of age the effects of the two drugs are the same as in the adult animals. In order to evaluate the development of the central cholinergic system, the activities of choline acetyltransferase and cholinesterases have been determined in whole brain, cerebellum, caudate nucleus and cerebral cortex in the different age groups. An increase is found in relative enzyme activity from birth up to adulthood. The changes in the effects of atropine and oxotremorine are discussed in relation to the development of the two enzymes, and to other biochemical, pharmacological, electrophysiological and behavioural data known for the dog. It is suggested that the change in sensitivity to the two drugs reflects the development of the central cholinergic system, which parallels the general development of the brain.