Michihiro Fujiwara

Mouse-killing behavior (muricide) induced by Δ9-tetrahydrocannabinol in the rat

Abstract Natural Δ 9 -tetrahydrocannabinol (THC) was found to induce a characteristic mouse-killing behavior (muricide) in rats upon chronic administration. In the rat housed individually, this muricide developed even on the first day of administration, and continued for a long period of time even after withdrawal of the drug.

Automutilation induced by clonidine in mice

Clonidine (2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride, St155, Catapres), after administration of a single large dose, was found to induce automutilation in mice housed individually in the absence of objects to bite. This abnormal behavior was not significantly altered with chronic administration of the drug, and showed no behavior induced by the same drug in mice caged in groups.

Noradrenergic involvement in catalepsy induced by Δ9-tetrahydrocannabinol

In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.

The course of aggressive behavior induced by a single injection of Δ9-Tetrahydrocannabinol and its characteristics

Abstract Female, Wistar King A rats subjected to one day of isolated housing, during which all food was withheld for 22 hr and supplied for only 2 hr, and then given a single dose of Δ 9 -tetrahydrocannabinol (THC) markedly exhibited muricide and rod-attack behavior. This continued for 100 days after treatment as far as the animals remained in isolation. They displayed rat pup-killing behavior as well, although normal virgin female rats did not show such behavior. When the rats were transferred from isolated housing to group housing 60 days after THC treatment, rod-attack behavior disappeared completely in all rats and muricide disappeared in 13 of the 28 rats which exhibited muricide. However, when these rats were returned to isolation after a 15 day period of group housing, rod-attack behavior and muricide identical to that observed previously reappeared. It is concluded that housing condition plays a crucial role in the occurrence and maintenance of THC-induced aggression including muricide.

Attack stress and IgE antibody production in rats

The effect of stress on production of immunoglobulin E (IgE) in rats was investigated, the IgE being titrated by passive cutaneous anaphylaxis (PCA) reactions. In rats, exposed to attack by other rats made aggressive by intraventricular injections of 6-OHDA for one hour per day for three consecutive days before the first immunization, there was no difference in the titer of IgE as compared to the control rats, but, in the rats exposed to stress procedure before the second immunization, the production of IgE was significantly suppressed.

Irritable aggression induced by delta 9-tetrahydrocannabinol in rats pretreated with 6-hydroxydopamine

Administration of delta 9-tetrahydrocannabinol (THC) to grouped rats injected intraventricularly with 6-hydroxydopamine (6-OHDA) produced violent fighting accompanied by remarkable hyperirritability. This behavior was induced reproducibly from the 10th to 100th postoperative days. It was shown that this irritable aggression could be measured continuously and quantitatively in terms of degree of activity and/or vocalization using a newly designed analyzer. The effect of THC differed markedly from the action of apomorphine and methamphetamine in 6-OHDA pretreated rats. Apomorphine induced irritable aggression but not vigorous vocalization. On the other hand, methamphetamine induced much less irritable aggression than apomorphine-induced aggression. It is assumed that a THC-invoked imbalance in catecholamine agonistic and serotonin antagonistic action brought about by activation of supersensitized catecholaminergic receptor was operating to produce the aggression. Specifically, hypoactivity of serotonergic neurons might play a key role in the occurrence of THC-induced irritable aggression.

Muricide induced by single injection of Δ9-tetrahydrocannabinol

Abstract Male rats were subjected to 22 hr of food deprivation and 24 hr of isolated housing and then Δ 9 -tetrahydrocannabinol (THC) was intraperitoneally injected. One hour after treatment, the dose-related muricide was observed. Next, the relationship between the duration of isolated housing and muricide was investigated. Regardless of the time at which THC was injected during periods of isolation ranging from 2 hr to 30 days, or even the animals were isolated concurrently to THC injection, muricide appeared at an incidence of 60–80%, and was unrelated to the duration of isolated housing. Muricide was not induced in communally housed rats treated with THC, but by placing these animals in isolation 1 hr after treatment, the time of peak effect of THC, muricide occurred in 70% of the rats. These results demonstrate that if the rat is placed in isolation within the period of the effect of THC, muricide is induced.

Autonomic drug effects and gastric secretion in a new experimental model of stress ulcers in rats

A psychological procedure which does not involve the application of physical stimulation was used to produce gastric ulcers experimentally. Ulceration was induced in rats by exposing the animals to the aggressive attacks of rats treated with 6-hydroxy-dopamine (6-OHDA). Gastric secretion and the effects of autonomic drugs on ulcer formation were investigated. Atropine methylbromide did not significantly inhibit the occurrence of erosions. Phentolamine or hexamethonium bromide significantly inhibited the production of erosions, and combined administration of an anticholinergic agents and alpha-blocking agent led to a complete inhibition, with no notable behavioral change. In case of pylorus ligation, gastric secretion during exposure to attack of 6-OHDA-treated rats was significantly less than that in the controls. We suggest that the sympathetic nervous system plays an important role in the production of gastric erosions, as induced by the methods reported in this study.

A new experimental model of stress ulcers employing aggressive behavior in 6-OHDA-treated rats

Abstract Rats receiving intraventricular injection of 6-hydroxydopamine (6-OHDA) were housed in isolation for one month and placed in the same cage as an untreated rat while being subjected to continuous tail pinching. 6-OHDA-treated rats violently attacked the untreated rat and stabilized fighting between the two animals persisted for over 1 hr. The 6-OHDA-treated rats consistently played the dominant role in the dominant-subordinate relationship established between the rats. By allowing this fighting to continue for 1 hr, gastric erosion associated with severe hemorrhage occurred with a high incidence in the untreated rats. These erosions were comparable in rats examined immediately after fighting and in those examined after 1 hr and 3 hr. Poststress rest was not required for erosion to occur. The presence of bite wounds incurred during fighting was unrelated to the incidence of gastric erosion. In addition, it was unnecessary to fast the untreated rats beforehand. Based on these findings, the present model apparently does not rely on physical stimulation. These factors and the ease of its execution make the present new experimental model of stress ulcers very useful.

Effects of psychotropic drugs on Δ9 long-lasting muricide

The effects of psychotropic drugs on THC-induced long-lasting muricide were investigated in rats. Changes in open field activity (ambulation and rearing) of the rat werre concurrently assessed as an index of behavioral toxicity. Imipramine-like antidepressants, atropine, and antiparkinsonism drugs exhibited a selective inhibitory activity on muricide, whereas the effects of neuroleptics, pentobarbital, diazepam, and methamphetamine were nonspecific. It is also suggested that cholinergic, catecholaminergic, and serotonergic mechanisms are involved in THC-induced muricide. This type of induced muricide appears to be a useful experimental model particularly suitable for the evaluation of antidepressants in correlation with brain amine dynamics.The effects of psychotropic drugs on THC-induced long-lasting muricide were investigated in rats. Changes in open field activity (ambulation and rearing) of the rat were concurrently assessed as an index of behavioral toxicity. Imipramine-like antidepressants, atropine, and antiparkinsonism drugs exhibited a selective inhibitory activity on muricide, whereas the effects of neuroleptics, pentobarbital, diazepam, and methamphetamine were nonspecific. It is also suggested that cholinergic, catecholaminergic, and serotonergic mechanisms are involved in THC-induced muricide. This type of induced muricide appears to be a useful experimental model particularly suitable for the evaluation of antidepressants in correlation with brain amine dynamics.