Decrease In Exploratory Behavior Research Articles

Behavioral effects on the progeny of mice treated with methylmercury

The effects of prenatal methylmercury (MeHg) exposure on the behavior of postnatal offspring were determined in 129 SvSl mice. A single dose of 0, 6, 8, or 12 mg/kg of methylmercury hydroxide (MeHgOH) was injected sc to pregnant mice on Day 10 of gestation. The following three types of behavioral tests were conducted on offspring from these mothers at various ages: (1) exploratory behavior by open-field test at age 23 days old, (2) spontaneous locomotor activity at ages 24, 44, and 64 days old, and (3) convulsive behavior to a convulsant, flurothyl at age 70 days old. Another group of 33-day-old offspring whose mothers had received three multiple doses of MeHgOH or daily doses of 0 or 4 mg/kg from Day 10 to Day 12 of gestation were also used for the open-field behavioral study. Results from the openfield test indicated that prenatal MeHg exposure decreases exploratory behavior as indicated by longer center square latency, lower number of peripheral squares traversed, lower frequency of rearing and grooming, lower frequency of urination, and higher frequency of backing, in treated groups in comparison to control groups. Depression in spontaneous locomotor activity was also observed in offspring prenatally exposed to MeHg; however, the effect diminished gradually as the animals grew older. In the flurothyl convulsion behavior test, it was found that animals prenatally treated with MeHg demonstrated significantly lower threshold to preliminary clonic convulsion as well as maximal clonic-tonic convulsion; thus, indicating an increase in susceptibility to flurothyl-induced convulsions. The observed decrease in exploratory behavior and spontaneous locomotor activity with an increase in convulsive susceptibility are not necessarily inconsistent findings and may be due to MeHg affecting two independent mechanisms. Therefore, it has been demonstrated that behavioral effects can be induced in offspring prenatally exposed to MeHg. Furthermore, behavioral effects of MeHg can be detected in offspring having no detectable gross congenital malformations.

Pharmacological Studies on Triazine Derivatives V. Sedative and Neuroleptic Actions of 2-Amino-4-[4-(2-Hydroxyethyl)-Piperazin-1-Yl]-6-Trifluoromethyl-s-Triazine (Tr-10)

Pharmacological properties of 2-amino-4-[4-(2-hydroxyethyl)-piperazin-1-yl]-6-trifluoromethyl-s-triazine (TR-10) were investigated in mice and rats. Chlorpromazine served as a reference compound. TR-10 expressed in general the pharmacological profiles as neuroleptics ascertained by anti-methamphetamine activity, supression of conditioned avoidance response, taming effects, decrease in exploratory behavior and cataleptogenic activity. Among these effects, anti-methamphetamine action was most potent. Different from chlorpromazine, TR-10 showed a similar pharmacological activity pattern in the intraperitoneal and oral routes of adminisstration as depicted from ED50/LD50 values. Although the effects relevant to neuroleptics were less potent than chlorpromazine, such were seen with TR-10 at lower doses than those causing muscle relaxation. TR-10 significantly depressed the spontaneous motor activity but showed no anti-convulsant action in mice. Hypothermic action, potentiating effects of hypnotics and α-adrenergic blocking action, characteristic to chlorpromazine, were very weak for TR-10. TR-10 also showed low toxicity in mice (LD50═820 mg/kg p.o., 465 mg/kg i.p.) compared with that of chlorpromazine (LD50 ═370 mg, kg p.o., 228 mg/kg i.p.).

Comparative behavioral effects of dibutyryl cyclic AMP and prostaglandin E 1 in mice

Three behavioral tests, spontaneous locomotor activity (SLMA), exploratory behavior (EB) and rotarod performance (RP), a measure of neuromuscular coordination, were used to study the interaction of PGE 1 (1 mg/kg i.p., 10 min. pretreatment) with DBcAMP (25 mg/kg i.p., 25 min. pretreatment) in mice. A dose-response relationship of PGE 1 (0.01–5.0 mg/kg) to SLMA was determined, with a significant decrease in SLMA produced by a dose of 0.1 mg/kg. Decreases in SLMA were produced by PGE 1 (79%), DBcAMP (41%) and DBcAMP-PGE 1 combination (71%). Similar decreases in EB were observed. Although no significant difference between controls and DBcAMP was observed in RP, 52% of mice tested were RP failures following PGE 1 and a 100% failure rate was induced by the combination. Mice were treated with a second injection of DBcAMP or PGE 1 or the combination 24 hr following the first injection. Behavioral activity of these mice was observed 25 min (DBcAMP) or 10 min (PGE 1) after the second dose was administered. A second injection of DBcAMP failed to decrease SLMA and EB from controls; moreover, SLMA began to return towards control levels as early as 2 hr between injections. The second injection of PGE 1 or DBcAMP+PGE 1 produced the same behavior as that produced by the first injection. On the basis of these results, the relationship of cyclic nucleotides and PGs to behavioral activity is discussed.

Biogenic amines and the effect of short term lithium administration on open field activity in rats

Experiments were performed to examine whether the effects of short-term lithium administration on cerebral biogenic amine metabolism might be related to its action on open field activity. Rats received intragastric injections of lithium chloride (1.5 mEq/kg) twice daily for 5 days. This lead to a decrease in exploratory behavior in the open field. Administration of imipramine, which blocks the efffects of short-term lithium administration on norepinephrine turnover and uptake in the brain, failed to influence the effect of lithium on exploratory activity. Parachlorophenylalanine, which inhibits cerebral serotonin synthesis and depletes brain catecholamines, prevented the behavioral effect of lithium. Injection of pargyline, which inhibits cerebral monoamine oxidase activity, counteracted the effect of lithium on exploratory behavior and also influenced the emotionality of the animals in the open field. The findings are consistent with the hypothesis that cerebral monoamine levels and monoamine oxidase activity play a role in the effect of short-term lithium administration on open field activity in rats.

Clozapine (W-801)の行動薬理学的ならびに脳波学的研究

The behavioral and electroencephalographic effects of Clozapine were investigated in mice, rats and rabbits, and compared with chlorpromazine and perphenazine. Clozapine showed in general the pharmacologic properties characteristic to neuroleptics, such as decrease in exploratory behavior, suppression of conditiond avoidance response, taming effects, anti-methamphetamine and so on. These effects were less potent and shoter in duration than those of chlorpromazine and perphenazine. Clozapine, however, lacked cataleptogenic propeties and depressed the EEG arousal responses induced not only by auditory but also by mesencephalic reticular stimulation, differently from chlorpromazine and perphenazine.