Head Twitches In Mice Research Articles

The inhibitory effect of methergoline on LAE-32-induced head-twitches in mice

Methergoline (a selective 5-HT blocker) was more powerful than chlorpromazine in inhibiting LAE-32-induced head-twitches in mice. Suggestions are made regarding the possible antihallucinogenic effect of this drug.

Effect of benzodiazepines on central serotonergic neuron systems

Intracerebral (i.c.) injection of serotonin (5-HT) into mice induced head twitches in a dose-dependent manner at 10 min after injection. The head twitches induced by 5-HT (i.c.) were potentiated by the pretreatment of isocarboxazid (3 mg/kg i.p.), and inhibited by cyproheptadine (0.3 mg/kg i.p.), a 5-HT antagonist. Benzodiazepines such as fludiazepam and diazepam potentiated the head twitches induced by 5-HT (i.c.) in a dose-dependent manner. Mescaline (50 mg/kg i.p.) also induced head twitches in mice at 15 and 30 min after injection. Benzodiazepines potentiated the head twitches induced by mescaline in a dose-dependent manner. Cyproheptadine blocked the potentiating effect of benzodiazepines on the head twitches induced by both 5-HT (i.c.) and mescaline. By repeated administration of fludiazepam or diazepam for 5 days, the potentiating effect of both drugs on the head twitches induced by mescaline was unchanged and their anticonvulsant effects were not modified. In contrast, the potency of both drugs on muscle relaxation was significantly decreased by repeated administration. Benzodiazepines failed to change the uptake of 5-HT into the synaptosomal fractions from the rat brain. These results suggest that the pharmacological action of benzodiazepines is derived at least in part from their activating effect on 5-HT receptors.

Effects of amitriptyline and isocarboxazid on 5-hydroxytryptophan induced head twitches in mice.

Effects of amitriptyline and isocarboxazid on brain 5-HT and 5-HIAA were examined in relation to their action on 5-HTP induced head twitches. Amitriptyline reduced 5-HTP induced head twitches but isocarboxazid increased them. Both amitriptyline and isocarboxazid caused a significant increase of brain 5-HT concentration in 5-HTP treated mice. Amitriptyline also caused a significant increase of 5-HIAA concentration, while isocarboxazid reduced 5-HIAA concentration in the brains of 5-HTP treated mice. Probenecid, which significantly increased 5-HIAA concentration without affecting brain 5-HT concentration in 5-HTP treated mice, reduced 5-HTP induced heat twitches. These results suggest that 5-HTP induced head twitches might be induced by an increase of 5-HT concentration, and reduced by an increase of 5-HIAA or a decrease of 5-HT concentration in the brains of mice.

Head twitches induced by benzodiazepines and the role of biogenic amines.

Clonazepam, one of the benzodiazepines, induced head twitches in mice in a dose-dependent manner and sustained them for at least 120 min. Some of the benzodiazepines such as nitrazepam, fludiazepam, and nimetazepam also significantly induced head twitches at doses higher than 10 mg/kg, but other benzodiazepines like diazepam, flurazepam, oxazepam, medazepam, and chlordiazepoxide did not significantly induce head twitches at doses up to 60 mg/kg. The head twitches induced by clonazepam were more strongly blocked by a n antiserotonin drug, cyproheptadine than catecholamine receptor blocking drugs, haloperidol, propranolol, and phentolamine, and were not blocked by GABA receptor blocking drugs, bicuculline and picrotoxin, as well as by a glycine receptor blocking drug, strychnine. Clonazepam also increased the head twitches induced by mescaline, a serotonin receptor stimulant. These results indicate that the head twitches induced by clonazepam might be mediated via serotonergic neuron systems.

Antagonistic effect of lithium carbonate on 5-hydroxytryptophan-induced head-twitches in mice

Lithium carbonate antagonized 5-HTP-induced head-twitches without influencing the rearings (“standing-up” reactions) and rotarod performance. Other antimanic drugs, haloperidol and phenigama (β-phenyl-γ-aminobutyric acid), suppressed head-twitches at doses which exert sedative action on rearings and rotarod performance. As distinct from antiserotonin compounds (BOL-148 and Deseril) Lithium did not counteract the serotonin-induced hypothermia or the peripheral effect of serotonin.

Behavioural effects of some morphine antagonists and hallucinogens in the rat.

Corne and Pickering1 found a good correlation between activity in inducing a behavioural response (head twitches) in mice and the hallucinogenic activity in man of several drugs, which included atropine, hyoscine, lysergide (LSD), mescaline, N,N-dimethyltryptamine, phencyclidine, psilocin and psilocybin. Drugs that did not cause head twitches in mice included the morphine antagonists cyclazocine (personal communication from S. J. Corne) and nalorphine, both of which are known to cause hallucinations in man2,3.

A possible correlation between drug-induced hallucinations in man and a behavioural response in mice.

The production of head-twitches in mice appears to be a suitable laboratory test for predicting whether a compound is likely to be hallucinogenic in man. This is based on the following findings: A potent antiserotonin, methysergide, antagonised the head-twitches induced by a wide variety of chemically different hallucinogens. This gives support to the idea that hallucinogens may act by mimicking, releasing or potentiating serotonin centrally.