A. Saner

Lysergic acid diethylamide: evidence for stimulation of cerebral dopamine receptors.

In the rat, lysergic acid diethylamide (LSD) decreased the striatal and retinal content of homovanillic acid. LSD did not change the level of dopamine (DA), but delayed the a-methyl-p-tyrosine-induced disappearance of this amine in the teldiencephalon. In the cat, LSD diminished the DA output into the perfusate of the caudate nucleus. Furthermore, LSD increased the activity of adenylate cyclase in striatal homogenates of rat. These and other findings indicate that in the central nervous system LSD stimulates DA receptors which may be involved in LSD-induced phychosis.

Effect of diazepam on cerebral 5-hydroxytryptamine synthesis

In the brains of normal and reserpinized rats both diazepam and amino-oxyacetic acid (AOAA) decreased the 5-hydroxytryptophan (5HTP) accumulation induced by the decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD 1015). In reserpinized animals, the action of diazepam was antagonized by picrotoxin and bicuculline in doses which did not themselves influence the NSD 1015-induced rise in 5HTP. In conclusion, diazepam probably depresses 5HT synthesis via GABAergic mechanisms and this effect is not dependent on a functionally intact monoaminergic synaptic transmission.

The effect of 5,6-dihydroxytryptamine on sexual behaviour of male rats

Abstract Injection of 5,6-dihydroxytryptamine (5,6-DHT) into the lateral ventricles of rats causes a marked increase in copulatory activity concomitant with a rather selective decrease of cerebral 5-hydroxytryptamine (5HT). 5-Hydroxytryptophan given i.p. counteracts both effects of 5,6-DHT. I.v. injection of 6-hydroxydopamine prior to 5,6-DHT causes a considerable decrease of brain catecholamines without enhancing the diminution of 5HT and, moreover, does not antagonize the copulatory activity. These results indicate that the 5,6-DHT-induced stimulation of copulatory behaviour in rats is correlated with a diminution in brain 5HT.

Decrease of dopamine and 5-hydroxytryptamine after intracerebral application of 5,6-dihydroxytryptamine

Summary Unilateral stereotaxic injections of 0.5–10 μg 5,6-dihydroxytryptamine (5,6-DHT) into the medial forebrain bundle (MFB) and the nigrostriatal dopamine (DA) bundle of rats caused a considerable decrease of 5-hydroxytryptamine (5-HT) and DA, but no or only a slight reduction of noradrenaline (NA) in the homolateral telediencephalon. On the contralateral side and in the caudal parts of the brain, no relevant diminution of the amines occured. The uptake of 5-HT and DA into brain slices and synaptosomes of the homolateral but not the contralateral telediencephalic regions was reduced. Application of 5,6-DHT in the dorsal NA bundle did not markedly affect the NA content of the telediencephalon. It is concluded that on intracerebral application 5,6-DHT does not show specificity only for the 5-hydroxytryptaminergic neurons, but also affects the dopaminergic system.

Cerebral monoamine metabolism in guinea-pigs with ascorbic acid deficiency.

Guinea‐pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair‐fed animals did not exhibit these changes. The α‐methyl‐p‐tyrosine (αMpT)‐induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair‐fed animals, but restored in guinea‐pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of αMpT) showed a decrease in both pair‐fed and ascorbic acid deficient animals. The noradrenaline of the heart exhibited a similar tendency. The αMpT‐induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without αMpT administration) decreased. Pair‐fed animals showed a similar tendency. The striatal concentration of homo‐vanillic acid (HVA) was diminished in both pair‐fed and ascorbic acid deficient guinea‐pigs. The cerebral content of 5‐hydroxy‐indoleacetic acid showed a decrease in pair‐fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under‐nutrition without ascorbic acid deficiency (pair‐feeding) diminishes the turnover of cerebral noradrenaline, 5‐hydroxytryptamine and striatal dopamine.

The action ofl-DOPA on sexual behaviour of male rats

Abstract In isolated male rats pretreated with repeated injections of l -DOPA or with an inhibitor of extracerebral decar☐ylase (Ro 4–4602), two successive doses of l -DOPA caused marked sexual stimulation when the animals were brought together. Simultaneously, a decrease of 5-hydroxytryptamine (5-HT) in the central nervous system occurred. l -5-Hydroxytryptophan antagonized the l -DOPA-induced sexual stimulation and elevated the decreased cerebral 5-HT levels. It is concluded that a decrease of 5-HT in the central nervous system is causally related to the l -DOPA-induced stimulation of sexual behaviour in rats and possibly also to the hypersexuality occasionally seen in patients with Parkinsons syndrome during l -DOPA treatment.

Enhancement of 5‐hydroxytryptamine synthesis in brain by monoamine‐depleting drugs

M O L L ~ ~ N ~ ~ ~ ~ ~ ~ , I., PEDERSEN, V., NYMARK, M., FRANCK, . F., BOECK, V., FJALLAND, B. & CHRISTENSEN, A. V. (,973). Actapharmac. lox., 33,353-362. V O I T ~ , K. & CUMMINGS, J. R. (1976). Can. J . Physiol. Pharmac., 54, 551-560. wlL~~MS, J. L. (1973). Naunyn-Schmiedebergs Arch. Pharmac., 279,115-126. yBH, B., MCNAY, J. L. & GOLDBERG, L. I. (1969). J. Pharmac. exp. Ther., 168,303-309. J. G . (1975). In: Advances in Neurology, Vol. 9, p. 177-184. Editors: Calne, D., Chase T. & Barbeau, A.

Accumulation of 5-HT in non-terminal axons after p-chloro-N-methylamphetamine without degeneration of identified 5-HT nerve terminals.

The effect of a single injection of d,1-p-chloro-N-methylamphetamine (PCMA) on 5-hydroxytryptamine (5-HT)- containing neurons in rat brain was investigated using fluorescence histochemical, electron microscopic and biochemical methods. PCMA caused in a dose-dependent manner (from 4.3 mg/kg), an increase of formaldehyde-induced indoleamine (IA) fluorescence in swollen non-terminal axons during the first 6 days and, in contrast, a diminution of IA fluorescence in nerve terminal regions for up to 42 days after treatment. These changes did not appear to be the result of destruction of 5-HT nerve terminals since at all time intervals investigated (12 h to 42 days), the fine structure and frequency of supra-ependymal 5-HT nerve terminals were unaffected. Moreover, no degenerating nerve terminals were observed in the suprachiasmatic nucleus. A marked transient decrease of IA fluorescence on day 2 in the 5-HT cell bodies B3-B9 was not followed by obvious morphological changes up to 42 days after PCMA. Therefore, the reduced 5-HT content of brain up to 42 days after treatment seems not to be due to a destruction of 5-HT neurons. Moreover, the damage to non-terminal 5-HT axons, as indicated by the 5-HT accumulation, seems not to be severe, at least not to those axons projecting to the cerebral ventricles and suprachiasmatic nucleus, since no degeneration of 5-HT nerve terminals was observed at any of the times investigated.

Increase of striatal dopamine turnover by drugs: Interference with granular storage or receptor blockade?

Apomorphine completely antagonized the reserpine-induced enhancement of the striatal 3,4-dihydroxyphenylalanine (dopa) accumulation seen after administration of the decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD 1015). Reserpine-like drugs, e.g. Ro 4-1284 and Ro 4-9040, markedly enhanced the striatal dopa accumulation (due to NSD 1015) in normal animals but not in rats treated with reserpine plus apomorphine. Haloperidol enhanced the striatal dopa accumulation to a similar extent in normal and in reserpine-apomorphine-treated animals. Chlorpromazine also caused an enhancement of striatal dopa accumulation in both types of animals, but its potency was somewhat higher in normal rats than in those treated with reserpine plus apomorphine. In conclusion, reserpinized animals treated with apomorphine appear to be useful models for differentiating whether a drug enhances striatal DA turnover by interference with granular DA storage or by blockade of DA receptors. The latter seems to be the main mechanism of action of neuroleptic drugs.