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At least 19 recordsLinked to original sources
PubMed1975

Hyperthermia induced by amphetamine, p-chloroamphetamine and fenfluramine in the rat-1.

Hyperthemia was elicited in rats by the subcutaneous injection of 4 mg/kg (+)-amphetamine, 4 mg/kg (+)-p-chloroamphetamine, or 8 mg/kg fenfluramine. This hyperthermia could be abolished by oral pretreatment with 300 mg/kg p-chlorophenylalanine. Cyproheptadine, at a dose of 0.05 mg/kg, completely inhibited the response induced by p-chloroamphetamine, but a dose of 0.4 mg/kg was necessary in the case of amphetamine and fenfluramine. Protection against hyperthermia by p-chloroamphetamine was also provided by chloroimipramine. Hypothalamic turnover of 5-HT was enhanced by all three amphetamines. alpha-Methyltyrosine and disulfiram had no effect on the hyperthemia induced by the amphetamines, FLA-63 seemed even to enhance it. Haloperidol, in the dose range of 0.1 -0.4 mg/kg, attenuated the hyperthermia induced by amphetamine and p-chloroamphetamine, but not that induced by fenfluramine. The results point to a central origin of the hyperthemia induced by amphetamine, p-chloroamphetamine and fenfluramine. In the mediation of this effect, 5-HT and, to a lesser degree, dopamine seem to play an important role.

Amphetamine↗
PubMed1978

5-Hydroxytryptamine: the effects of impaired synthesis on its metabolism and release in rat.

1 Control rats given L-tryptophan (100 mg/kg) showed a smaller increase of brain 5-hydroxytryptamine (5-HT) than its metabolite 5-hydroxyindoleacetic acid (5-HIAA). However, when brain 5-HT concentrations were depleted by 40-50% after treatment with the synthesis inhibitor p-chlorophenylalanine (PCPA) (150 mg/kg) L-tryptophan caused a considerable increase in 5-HT but no change in 5-HIAA. Similar results were obtained following depletion of brain 5-HT by pretreatment with p-chloroamphetamine (10 mg/kg).2 Electrical stimulation of the median raphe nucleus of control rats significantly increased 5-HIAA in the hypothalamus, hippocampus and striatum. However, stimulation of PCPA (200 mg/kg) pretreated animals did not significantly increase 5-H1AA either 24 or 72 h after administration of the drug.3 Pretreatment of rats with PCPA (200 mg/kg) increased striatal synaptosomal uptake of [(3)H]-5HT by 30% and reduced 5-HT concentration in the rest of the brain by 62%.4 PCPA (150 mg/kg) markedly reduced the acute behavioural response (-76%) to p-chloroamphetamine (10 mg/kg) although brain 5-HT was only moderately reduced (-36%). L-Tryptophan (100 mg/kg) given 15 min before p-chloroamphetamine restored both brain 5-HT and the behavioural effects of p-chloroamphetamine in PCPA pretreated rats and enhanced the behavioural response to p-chloroamphetamine in control rats.5 The results suggest that newly synthesized 5-HT is less rapidly metabolized in rats with low brain 5-HT. The possible reasons for this and the relevance of the results to the use of L-tryptophan in the treatment of depressive illness are discussed.

Animals↗
PubMed1975

P-Chloramphetamine: Selective neurotoxic action in brain.

Injection of 2.5,5, 10, or 20 milligrams of p-chloroamphetamine per kilogram of body weight into rats produced evidence of cytopathological changes in sections of brain stained by a Nissl or silver method. As early as 1 day after drug injection cells demonstrated an intense Nissl staining, intense argyrophilia, cellular shrinkage, and perineuronal spaces. At 30 days after injection both stains revealed cellular debris and glial reactions characteristic of cellular dissolution. The neurotoxic effects of 2.5, 5, or 10 milligrams of p-chloroamphetamine per kilogram were primarily restricted to an area of the ventral midbrain tegmentum corresponding to the distribution of the B-9 serotonergic cell group. After 20 milligrams of p-chloroamphetamine per kilogram there was also evidence of neurotoxic effects on cells within the substantia nigra. These results confirm previous suggestions that the long-term reduction in serotonin content of brain, tryptophan-5-hydroxylase activity, and uptake of serotonin after injection of p-chloroamphetamine is due to a neurotoxic effect of the drug or some metabolite on serotonergic cell bodies.

Amphetamine↗
PubMed1978

Generalization study with some narcotic and nonnarcotic drugs in rats trained for morphine-saline discrimination.

Rats were trained to lever-press on an FR-10 schedule for food reinforcement, and to respond differentially on two levers while discriminating the effects of morphine (10 mg/kg) injection from those of saline (1 ml/kg). Following discrimination training, the morphine stimulus was generalized to propoxyphene, methadone, fentanyl, and sulfentanyl in a dose-dependent manner, and saline was generalized to alcohol, pentobarbital, azaperone, clonidine, naloxone, and p-chloroamphetamine. p-Chloroamphetamine failed to block the morphine stimulus.

Animals↗
PubMed1978

The effect of lysergic and diethylamide (LSD) and 2-bromolysergic acid diethylamide (BOL) on the striatal DOPA accumulation: influence of central 5-hydroxytryptaminergic pathways.

Selective chronic lesions of the dorsal raphe nucleus or combined lesions of the dorsal and median raphe nuclei did not significantly change the in vivo tyrosine hydroxylation in the striatum as measured by the DOPA accumulation after decarboxylase inhibition. Neither did acute combined lesions of the raphe nuclei, nor did electrical stimulation of the dorsal raphe nucleus have any significant effect. p-Chloroamphetamine (PCA, 20 mg/kg, i.p.) and p-chlorophenylalanine (PCPA, 400 mg/kg, i.p.), known inhibitors of the 5-hydroxytryptamine (5-HT) synthesis, significantly decreased the DOPA accumulation. The increase in DOPA accumulation observed after LSD (0.5 mg/kg, i.p.) or BOL (0.5 mg/kg, i.p.) was seemingly unaffected by pretreatment with PCA or PCPA and also after lesion of the dorsal raphe nucleus. The results suggest that the effect of LSD or BOL on the DOPA accumulation in the striatum is not mediated via a 5-hydroxytryptaminergic control mechanism originating in the dorsal raphe nucleus. A control mediated via the median raphe nucleus cannot be excluded, since LSD did not increase the DOPA accumulation after combined chronic raphe lesions. Such a control would also be in agreement with our previous results suggesting that hte DOPA generation after LSD is controlled by 5-HT receptors.

Animals↗
PubMed1979

Is a dopaminergic system involved in thyrotropin releasing hormone induced hyperthermia and in its potentiation by amphetamine?

1. A dose-related hyperthermia is obtained in mice with TRH administered intraperitoneally. 2. This hyperthermia is reinforced by amphetamine given at doses which usually cause hypothermia. 3. p-Chloroamphetamine and L-Dopa also reinforce TRH hyperthermia. Apomorphine is not significantly active. 4. TRH hyperthermia is lowered significantly by alpha-methyl-tyrosine and haloperidol but not significantly by pimozide and chlorpromazine. TRH + Amph hyperthermia is not lowered by any of the DA antagonists tested even at doses reversing Amph hyperthermia. Direct participation of DA receptors is then doubtful. 5. All these variations of temperature have their acme a 15 min except for reserpine which, given 22 hours before, potentiates TRH + Amph hyperthermia after 30 min.

Amphetamine↗
PubMed1979

p-Chloroamphetamine-induced hyperthermia pharmacologically distinct from fenfluramine-induced hyperthermia.

The influence of various drug pretreatments upon the responses of rabbits to the putative indirect 5-hydroxytryptaminergic agonists p-chloroamphetamine (PCA) and fenfluramine were examined. In naive rabbits PCA evoked hyperthermia, behavioural excitation and prominent forepaw clonic activity, while fenfluramine produced only hyperthermia and behavioural stimulation. The hyperthermic and behavioural responses of both agents were reduced by the 5-hydroxytryptamine (5-HT) uptake inhibitor, fluoxetine, potentiated by the monoamine oxidase inhibitor, pheniprazine, and unaltered by the dopaminergic antagonist, haloperidol. Pretreatment with the 5-hydroxytryptaminergic receptor blockers cinanserin, cyproheptadine or D-2-bromolysergic acid diethylamide markedly attenuated the effects of fenfluramine but only slightly influenced the responses to PCA. Depeletion of central 5-HT stores with p-chlorophenylalanine also affected responses to fenfluramine more than responses to PCA. The tryptaminergic receptor blocker methergoline abolished both PCA-induced hyperthermia and forepaw clonus--but not behavioural stimulation--while the effects of flenfluramine were only partly reduced. We interpret these data to mean that PCA- and fenfluramine-induced drug effects have different underlying mechanisms, the PCA responses relying possibly upon tryptamine while the fenfluramine responses are 5-hydroxytryptaminergic.

Amphetamines↗
PubMed1979

Serotonergic function in mouse head twitches induced by lithium and reserpine.

We examined the relationship between lithium-induced head twitches and serotonergic neurons. Head twitches were elicited by combined treatment with lithium chloride (2 or 5 mEq/kg x 5, s.c. administered hourly) and rauwolfia alkaloids, i.e., reserpine (5 mg/kg, s.c.), tetrabenazine (20 mg/kg, s.c.), and syrosingopine (10 mg/kg, s.c.). Neither lithium nor the alkaloid alone induced the twitches; nor did combined administration of lithium with methamphetamine or p-chloroamphetamine. The head twitches induced by lithium in combination with reserpine were strongly inhibited by antiserotonin drugs, methysergide and cyproheptadine, and also by a serotonin synthesis inhibitor, p-chlorophenylalanine (PCPA), when administered between lithium and reserpine. When PCPA was administered before lithium for 3 days, the head twitches were potentiated. In addition, the head twitches were potentiated by a serotonin receptor stimulant, 5-methoxy-N,N-dimethyltryptamine. The results imply that lithium can induce head twitches in the presence of rauwolfia alkaloids and may exert its effect in part by acting on the serotonergic neuron system.

Acetylcholine↗