COCAINE--EFFECTS ON SINGLE NEURONS

Cocaine is known to act on amine containing neurons to inhibit
uptake of transmitters. The reuptake of noradrenaline, 5-HT and
dopamine is inhibited, but it is not known whether these
mechanisms are equally sensitive to cocaine in intact functioning
neurons. It is proposed to compare and contrast the action of
cocaine at sites in brain which contain each of these
neurotransmitters. Intracellular recordings from neurons in four
amine containing nuclei; the locus coeruleus, dorsal raphe,
substantia nigra and ventral tegmental area will be made in
submerged brain slices in vitro at 37 degrees C. The choice of
these nuclei is based on the compact structure, biochemical
homogeneity and the presence of amine receptors on the cell
bodies of the neurons contained in each of the nuclei. Neurons in
each of the four nuclei are similar in that they possess receptors
for the same transmitter which they produce, 'autoreceptors'.
These nuclei differ however in the type of 'autoreceptor', the
number of other amine receptor subtypes and the afferent
innervation from other amine containing nuclei. The effects of
cocaine on the membrane properties, the actions of exogenously
applied substances (noradrenaline, 5-hydroxytryptamine and
dopamine) and synaptically released transmitters (noradrenaline,
5-hydroxytryptamine and dopamine) will be determined in these
major amine containing nuclei. By investigating the action of
cocaine of neurons in four amine containing nuclei the proposed
studies will significantly increase our understanding of cocaine
actions in the central nervous system. From these studies it
should be possible to determine the cellular mechanisms and sites
which are involved in the psychotomimetic actions of cocaine, and
perhaps in the dependence liability which cocaine is now
recognized to possess.