The main aim of this work was to investigate the role of central cholinergic mechanisms in the control of behaviour. Three strains of rat, which display behavioural differences, were chosen for use in the work, these were the Roman High Avoidance (RHA) and the Roman Low Avoidance (RLA) strains, with the Porton strain to act as a reference line. Differences in conditioned avoidance behaviour and spontaneous activity were demonstrated between the strains and also in their behavioural response to drugs known to affect the central cholinergic system. These were, an anti-acetylcholine drug, N-ethyl-3-piperidyl benzilate which produced hyperactivity and facilitated avoidance conditioning, an anti-cholinesterase drug, physostigmine, which depressed spontaneous activity and conditioned avoidance behaviour. No change in behaviour of any of the strains was seen after treatment with drugs thought to have mainly peripheral actions on the cholinergic system. These drugs were N-ethyl-3-piperidyl benzilate methiodide and pyridostigmine. Strain differences were also seen in response to an adrenergic drug, d-Ampheta-mine. Facilitated behavioural performance was seen after a combination of anti-acetylcholine and adrenergic drugs were given to rats, which when given separately, at the same doses, produced no effect on behavior. Determination of acetylcholine concentration and cholinesterase activity in discrete brain areas revealed differences in the former but not the latter activity, implying that differences also exist between the strains in enzyme to substrate ratios. The support these findings give to theories of cholinergic inhibition in the control of behaviour and to the idea that behavioural control results from the central interaction of cholinergic and adrenergic transmitter systems is discussed. The value of selectively bred strains as tools in psychopharmacology is also assessed in the light of this work.
|Date of Award||1974|