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H R Frischknecht

Publications and source records attributed to H R Frischknecht.

30 records · Page 2Linked to original sources

Defeat, learned submissiveness, and analgesia in mice: effect of genotype.

Defeat-induced unconditioned and conditioned behaviors of C57BL/6 and DBA/2 mice were assessed in a social-learning paradigm. Upon bites, mice of the DBA strain reacted with significantly more escape reactions, while C57 mice showed more immobility, crouch, and defensive sideways and upright postures. Clear genotype-dependent patterns were also evident from the conditioned responses recorded 24 h after defeat. DBA mice displayed more escape and defensive sideways and upright postures upon contact with a nonaggressive partner mouse; in contrast, C57 mice reacted with more immobility and crouch. With an increasing number of bites the sum of learned responses increased in C57 mice while it decreased in mice of the DBA strain. This decrement was paralleled by an increase in the analgesic response measured on the hot plate in defeated DBA mice. The possible role of endogenous opioids in the genotype-dependent interaction of defeat-induced learned submissiveness and analgesia is discussed.

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Inhibition of morphine-induced analgesia and locomotor activity in strains of mice: a comparison of long-acting opiate antagonists.

The long-acting opiate antagonistic potency of naloxazone (NXZ), beta-chlornaltrexamine (beta-CNA) and beta-funaltrexamine (beta-FNA) was compared using three inbred strains of mice, in which morphine induces either analgesia (DBA/2), locomotion (C57BL/6), or both responses (C3H/He). The antagonists were applied SC 24-120 hr before morphine (10 or 20 mg/kg, IP), followed by the tests after 30 min. The minimal dose which completely antagonized morphine-induced analgesia in DBA and locomotion in C57 mice during 24 hr were: for NXZ 50 and 100 mg/kg, for beta-CNA 0.8 and 6.2 mg/kg, for beta-FNA 1.6 and 12.5 mg/kg, respectively. beta-FNA and beta-CNA more potently blocked morphine-induced analgesia in DBA mice than the activity response in the C57 strain. In contrast, beta-FNA prevented morphine-induced locomotion at a lower dose (6.2 mg/kg) than analgesia (greater than 50 mg/kg) in C3H mice, while beta-CNA was equipotent (1.6 mg/kg). In general, beta-CNA turned out to be the most reactive compound, antagonizing morphine effects in low doses up to 120 hr. beta-FNA selectively antagonized either morphine-induced analgesia or locomotion, depending on the strain used. This suggests that a given morphine response might be caused by a genetically determined multiplicity of opiate receptor types and their mutual interactions.

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Behavioural effects of hashish in mice in comparison with other psychoactive drugs.

1. The behavioural effects of hashish extract (10 mg delta 9-THC/kg) were compared to those of morphine (20 mg/kg), diazepam (10 mg/kg), imipramine (10/kg), amphetamine (10 mg/kg) and chlorpromazine (10 mg/kg) by testing male mice in a resident-intruder situation. 2. The drugs were given either to the resident or to the intruder male. 3. Hashish extract similar to diazepam and chlorpromazine reduced social activities in resident and intruder males. 4. Intruder males treated with hashish or diazepam were more frequently attacked and submission and light was increased. 5. Amphetamine and morphine stimulated locomotion and non-social activities but impaired social behaviour especially in residents. 6. Imipramine increased aggressive behaviour in resident and intruder males.

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Effects of multiple, chronic and early hashish exposure on mating behavior, nest-building and gestation in mice.

1. The effects of hashish extract on social behavior were investigated in pairs of mice living together from mating to parturition. The drug was administered orally to both animals at a dose of 20 mg delta 9-tetrahydrocannabinol/kg three times a week, either (I) during the 3 weeks from mating to parturition, (II) during the 12 weeks from weaning to mating and parturition, or (III) only during the 3 weeks after weaning. 2. In the mating tests, an acute administration (I) caused a general sedation. Chronically treated animals (II) showed decreased sexual behavior and lower social investigations despite significantly more non-social activities. Early drug treatment (III) had no effect on mating behavior. In all three series of experiments the females had conceived by the next morning. 3. The nest-building behavior during pregnancy was suppressed after multiple (I) and chronic (II) drug administration. In early drug-treated animals (III) the transport of nesting material was only slowed down. Non-social activities were normal or increased in all three series. 4. Parturition was significantly delayed by one day after multiple (I) and chronic (II) drug administration. The birth weight was not affected, but the litter size was decreased after chronic drug treatment. Early drug administration (III) had no effects on these parameters. 5. In conclusion, whereas tolerance to the sedative effects of hashish developed very rapidly, the drug influences on social behavior were stable. Therefore, discussions on legalization of cannabis should pay attention to the drug effects on social behavior.

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Behavioral effects of hashish in mice. IV. Social dominance, food dominance, and sexual behavior within a group of males.

Within groups of three adult male mice the acute and subchronic effects of hashish extract (20 mg delta 9-THC/kg) on social dominance, food dominance, and sexual interactions with a female were investigated. An initial drug treatment of only the dominant male weakened his social position, but dominance was regained after treatment 2 or 3. In contrast, a persistent change in dominance was found when only the male which was dominant in the feeding test was treated with the extract. Simultaneous drug treatment of all three males did not affect the social dominance relationship but resulted in a reversible change in food dominance. The original feeding order was reestablished after drug treatment 3. Upon meeting an estrous female, no male of the group was distinctly dominant in mating. After treatment 1 was given to all members of the group, all types of behavior were impaired and total activity was significantly reduced. After treatment 2, animals showed tolerance to the sedative effects, and after treatment 3, sexual behavior was even more frequent in drugged animals than in controls. The results are discussed in relation to a possible dependence of behavioral drug effects and tolerance development on the experimental situation.

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Behavioral effects of hashish in mice. III. Social interactions between two residents and an intruder male.

The acute and subchronic effects of hashish extract (20 mg delta 9-THC/kg) on the social interactions between two drug-treated residents and an untreated intruder male were investigated. In this analysis 28 different behavioral elements were recorded. A single drug application suppressed all categories of behavior, except submissive behavior and flight, in dominant and subordinate residents. Treated animals were less active than controls and immobility was very frequent. An elevated total activity, due to an increase in non-social activities, was observed in the untreated intruder males of this group. Social investigation as well as submissive behavior and flight were reduced in these animals. On introduction of an untreated male after the fourth drug treatment of the residents, the drugged males showed tolerance to the sedative and most of the other behavioral effects of the drug, and intruder males behaved quite normally. The formation of a dominant-subordinate relation within the group was influenced neither by a single nor by repeated drug treatment. The acute and subchronic effects of hashish extract on social, especially aggressive behavior of males are compared to those described in previous papers and the variation in the results of the different studies is discussed.

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Behavioral effects of hashish in mice. I. Social interactions and nest-building behavior of males.

The acute and subchronic effects of hashish extract (20 mg delta 9-THC/kg) on the behavior of male mice encountering a control partner was studied by ethological methods. A single administration of the extract resulted in general sedation, suppressing all the individual and social activities with the exception of some submissive elements. The locomotive and the overall activity of drugged males was drastically reduced and immobility occurred frequently. After four applications, tolerance to the sedative effects had developed and behavioral drug effects were recognizable. Drugged males showed an increase in nonsocial activities as well as in submissive behavior and flight, whereas social investigation was less frequent. Sexual and aggressive behavior was not significantly affected by the drug and immobility no longer occurred. In spite of behavioral changes after a single or repeated drug treatment, drugged males became dominant in about half the experiments. The nest-building behavior of males was disturbed in the same way after one or four drug applications. Drugged males generally refrained from carrying and working up the nesting material. The acute behavioral effects of hashish extract are compared to those described in previous papers and the difference between acute and subchronic drug effects is discussed.

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Behavioral effects of hashish in mice. II. Nursing behavior and development of the sucklings.

Adult mice were treated from parturition to weaning of their first litter with a hashish extract containing 40% delta 9-tetrahydrocannabinol (delta 9-THC), 45% cannabidiol, 9% cannabinol, and 6% other cannabinoids. Oral administrations of 20 mg delta 9-THC/kg three times a week decreased the weight gain of pups from days 3-6 and 6-10 significantly, resulting in about 15% lower body weights on days 6 and 10 compared with control sucklings. Other parameters of development such as the general appearance of the pups were little affected, except for a slight tendency by day 13, when some additional control pups already had both eyes open. The effects of hashish in sucklings might be caused by drug intake with mother's milk, as well as by a decreased lactation of drugged dams. In addition, our pup retrieving tests at the day 3, 1.5-2 h after the second application of hashish extract, showed a decrease in the mother's locomotive and nonsocial activities and pointed to at least transient impairment of the maternal behavior. By day 10, after the fifth administration of hashish extract, a partial tolerance occurred, with normal care for the young, but still decreased nonsocial activities of the drugged dams. Thus our experiments showed distinct effects of cannabis on mice litters when the parents were drugged postnatally during the period of lactation only.

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