Some Behavioural Interactions between 5-Hydroxytryptamine and Dopamine
Behavioural interactions between dopamine (DA) and 5-hydroxytryptamine (5HT) were studied using a stimulus (tail-pinch) and a drug (d-amphetamine) both of which cause release of DA. This release was confirmed by voltammetry. Various drug experiments indicate that the behavioural response to tail-pinch and some well known behavioural responses to amphetamine (rearing, gnawing) are attenuated by 5HT. Thus, the above behavioural effects were both decreased by the 5HT releaser p-chloroamphetamine. Also the effect of amphetamine was increased when 5HT synthesis was inhibited or when 5HT receptors were blocked.
Another behavioural pattern, backward-walking and circling, occurs when d-amphetamine, p-chloroamphetamine or fenfluramine are given either singly at high dosage or together at lower dosage so that both DA and 5HT are presumably simultaneously released. 5HT appears to be required for this behaviour when provoked by amphetamine as it was intensified by tryptophan and attenuated if 5HT synthesis was inhibited or 5HT receptors were blocked. The requirement of DA for backward-walking was shown by its attenuation by neuroleptics which occurred at lower neuroleptic concentrations than required for concurrent blockade of conventional 5HT-dependent behaviours (hind-limb abduction, etc.).
The results are discussed in relation to other reported behavioural interaction between DA and 5HT. Their possible relevance to hallucinogenic activity, amphetamine psychosis and schizophrenia is commented on.
The enormous effort that has gone into the study of the behavioural roles of individual transmitters has so far led to no more than partial understanding. This largely reflects the manifold roles of these substances and also the limitations of methods used for studying their relationships with behaviour. Almost all work done on these problems has involved disturbing transmitter function either by giving drugs or by destroying part of the transmitter containing system. Both approaches frequently involve uncertainties of specificity and as they have almost invariably been used to produce gross changes of transmitter function the associated behavioural changes may thus be of limited physiological significance. Furthermore, because these changes have often been assessed by methods which included different behaviours within a single general category significant relationship between transmitters and specific behavioural components may have been obscured.
Difficulties are compounded in attempts to study not merely the behavioural roles of single transmitters but behavioural interactions between different transmitters. However, it is obvious that this must be attempted as individual transmitters are hardly likely to exert their effects in isolation. This paper will centre on some interactions between dopamine (DA) and 5-hydroxytryptamine (5HT) we have recently been working on — in particular, investigations of the effect of 5HT on behavioural responses to a stimulus (tail-pinch) and a drug (d-amphetamine) which both cause DA release. Results illustrate different kinds of behavioural interaction between these two transmitters. We find that response to tail-pinch and some well known behavioural effects of amphetamine such as rearing and gnawing appear to be attenuated by 5HT but another behavioural pattern — backward-walking (retropulsion) and circling — appears to require concurrent release of both transmitters.
KeywordsBehavioural Interaction Forward Walking Individual Transmitter Raphe Lesion Median Raphe Lesion
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