Backward Walking and Circling: Behavioural Responses Induced by Drug Treatments Which Cause Simultaneous Release of Catecholamines and 5‐hydroxytryptamine

Abstract

The roles of catecholamine and 5-hydroxytryptamine (5-HT) release in mediating backward walking and circling were studied in rats. 2 These behaviours occurred in animals given 15 mg/kg intraperitoneally of (+)-amphetamine (which predominantly releases catecholamines) or either p-chloroamphetamine or fenfluramine (which predominantly release 5-HT). They also occurred when smaller doses of (+ )-amphetamine (5 mg/kg) and either p-chloroamphetamine (2-5 mg/kg) or fenfluramine (5 mg/kg) were given together. 3 Characteristic dopamine-dependent behaviours (rearing, licking, gnawing) resulting from (+)-amphetamine injection were greatly reduced by p-chloroamphetamine or fenfluramine. 4 Characteristic 5-HT-dependent behaviours (wet dog shake, hind limb abduction) resulting from injection of either p-chloroamphetamine or fenfluramine were unaffected by (+)-amphetamine. 5 Fragmentary backward walking and circling resulting from levallorphan injection (50 mg/kg s.c.) were decreased by (+)-amphetamine at low dosage. 6 Results in general strengthen previous evidence that backward walking and circling are mediated by simultaneous dopamine and 5-HT release. 7 The possible relevance of the above findings to hallucinogenic activity, amphetamine psychosis, schizophrenia and abnormal movements due to L-DOPA treatment is discussed.

Increased Central 5‐hydroxtryptamine Receptor Mechanisms in Rats After Chronic Neuroleptic Treatment

“…Neuroleptic-treated animals and control rats were treated side by side. The following 5-HT-dependent behaviours were scored (see Grahame-Smith, 1971;Curzon, Fernando & Lees, 1979): head bobbing and lateral head weaving, Straub tail, reciprocal forepaw treading, tremor, backward walking and body writhing movements. 'Wet-dog' shakes (Bddard & Pycock, 1977) were counted in a 1 min period.…”

“…Whilst it is likely that many of the behaviours observed do not solely reflect 5-HT function but will also involve other neurotransmitter systems such as the catecholamines (e.g. Curzon et al, 1979;see below), these drugs also enhanced 'wet-dog' shake behaviour in neuroleptictreated animals, a model which appears to depend mainly on 5-HT mechanisms (Bedard & Pycock, 1977).…”

“…Although we believe that the behaviours quantified in this study basically reflect central 5-HT function, the enhanced dopaminergic component may have contributed to some of the motor responses observed. For example, stereotyped sniffing is usually associated with stimulation of striatal dopamine receptors and it is known that drugs such as 5-HTP and fenfluramine can displace dopamine from presynaptic terminals (Curzon et al 1979). Therefore, a certain degree of caution should be exercised when interpreting some behavioural patterns.…”

“…However. 5-HT agonists or drugs which elevate synaptic 5-HT concentration are known to produce abnormal motor behaviour (Curzon et al, 1979). Therefore, in view of the fact that enhanced 5-HT receptor function apparently occurs after neuroleptic treatment it should be considered that tardive dyskinesias may in part be related to the formation of supersensitive 5-HT receptors.…”

Decreased accumulation of brain 5-hydroxytryptophan after decarboxylase inhibition in rats treated with fenfluramine, norfenfluramine or p-chloroamphetamine

“…These chemically similar agents are believed to affect 5-HT neurons through similar mechanisms and generally produce similar effects on 5-HT concentrations (see Fuller et a1 1978, for references) and function (Trulson & Jacobs 1976;Curzon et al 1979;Fuller & Snoddy 1980;Fuller & Clemens 1981). Costa et a1 (1971) and Costa & Revuelta (1972a) reported increased turnover of tel-diencephalic 5-HT (increased specific activity of brain 5-HT after injection of radioactive tryptophan) shortly after treatment with fenfluramine or norfenfluramine, but decreased 5-HT turnover after p-chloroamphetamine (Costa & Revuelta 1972b).…”