The effect of the sympathomimetic amines on behaviour and electrocortical activity of the chicken

Abstract

1. 1. Using a technique developed for recording cerebral electrical activity in conscious unrestrained small animals, the change of electrocortical activity with maturation of the chick was studied. There was a high correlation between the type of electrocortical activity and behaviour even in the newly-hatched chick. The alteration in effect of a number of sympathomimetic amines on electrocortical activity and behaviour was also examined with respect to maturation. 2. 2. In 1–28 day old chicks a triple structure activity division of the sympathomimetic amines for their effect on electrocortical activity and behaviour was possible. Thus amines (Group 1) with two -OH groups on the aromatic nucleus (adrenaline, noradrenaline, isoprenaline, cobefrine and dopamine), or amines with one -OH group on the benzene ring and one -OH on the β-carbon atom of the side-chain (phenylephrine) produced electrocortical slow wave activity and sleep. The changes were identical to those produced by the central depressant, pentobarbitone sodium. Electrocortical and behavioural sleep was also occasionally elicited by the 3-methoxy analogues of adrenaline and noradrenaline, metanephrine and normetanephrine. Sympathomimetic amines (Group 2) with one -OH group on the benzene ring (pholedrine, tyramine) had equivocal effects on behaviour or electrocortical activity. Of the amines with one -OH group on the β-carbon atom, pipadrol regularly elicited a behavioural and electrocortical alerting, whereas ephedrine occasionally produced behavioural and electrocortical sleep. Phenylethylamines with no -OH groups on the benzene ring or side-chain (Group 3) such as amphetamine, methyl phenidate, or phenmetrazine produced electrocortical and behavioural arousal from the first day of life. A characteristic behavioural pattern of increased rate of chirping and stereotyped motor activity developed after amphetamine in the young but not in the mature chicken. Behavioural electrocortical arousal was also produced by the aliphatic amine tuaminoheptane. 3. 3. On the basis of these and other results it appeared that in the young chick, the amphetamine-like substances produced their effect neither by the central release of noradrenaline nor by a central action on adrenaline or noradrenaline receptors. 4. 4. By the 4th week of life, the chicks response to the sympathomimetic amines altered, a transitional electrocortical pattern (alternation of slow wave and fast activity) being produced. Behaviourally the animal was usually drowsy or asleep. By the 3rd month all the amines tested except for β-phenylethylamine, methoxamine, epinine, and the adrenaline and noradrenaline metabolites, consistently produced behavioural and electrocortical alerting. 5. 5. Nicotine, which is a potent liberator of adrenal hormones, produced slow wave activity in young chicks with superimposed “spikes” of 150–200 μV. In adult birds, low voltage fast electrocortical activity appeared after nicotine with frequent “spikes” of 200–250 μV. 6. 6. The change in effects of the sympathomimetic amines with the chicken's development was related to maturation of the blood brain barrier, and also to the possibility that in the young chick the Group 1 amines produced sleep not by a central depressant chemical action but rather by the activation of central inhibitory mechanisms. 7. 7. The threefold division of the sympathomimetic amines found with the 1–28 day old chick was integrated with the similar threefold structure activity division of the amines that can be made with in vitro smooth muscle or denervated in vivo smooth muscle receptors.