Development of Synaptic Substrates for Drug Actions in Immature Brain
Studies of the effects of drugs and hormones on the immature brain must of necessity proceed from an understanding of the nature of the neural and synaptic substrate that constitutes the primary target of action of the pharmacological agent under investigation. Unfortunately this has rarely been possible for the obvious reason that there is a paucity of data available on the organization and properties of different subsystems during the development of the central nervous system in different species. Development implies change, and this cardinal feature of maturation introduces variables in the assessment of drug action in immature animals which may be major determinants of overt effects. An instructive example of the manner in which the developmental processes may influence drug actions is illustrated in Fig. 1 which summarizes data obtained over a decade ago in studies of the effects of topically applied aliphatic ω-amino acids on the immature brain (Purpura, 1961a). In these studies local responses elicited by cortical surface stimulation were utilized to determine the responsiveness of axodendritic synaptic pathways (Purpura, 1961b) to ε-amino caproic acid, a six-carbon aliphatic ω-amino acid which in adult animals produces rapid potentiation of superficial negative responses and subsequent convulsant activity (Purpura et al., 1959).
KeywordsFunctional Development Postnatal Development Thalamic Neuron Convulsant Activity Spike Potential
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