Biomedical subjects
H Rigter
Publications and source records attributed to H Rigter.
GABA-B receptor activation and conflict behaviour.
Baclofen and oxazepam enhance extinction of conflict behaviour in the Geller-Seifter test while baclofen and diazepam release punished behaviour in Vogel's conflict test. In order to investigate the possibility that the effect of the selective GABA-B receptor agonist baclofen is mediated indirectly via the GABA-A/benzodiazepine receptor complex, the effect of pretreatment of rats with baclofen on [3H]-diazepam binding to washed and unwashed cortical and cerebellar membranes of rats has been studied. Baclofen pretreatment increased Bmax in washed cerebellar membranes when bicuculline was present in the incubation mixture. No effect was seen in cortical membranes. The present results render it unlikely that the effect of baclofen on extinction of conflict behaviour and punished drinking is mediated via the GABA-A/benzodiazepine receptor complex.
Antagonism of effects of vasopressin (AVP) on inhibitory avoidance by a vasopressin antagonist peptide [dPtyr(Me)AVP].
After training in two different passive avoidance tasks, the platform box of Ader and De Wied (1972) and the Jarvik box of Jarvik and Kopp (1967), rats injected with vasopressin immediately following the training trial showed a significant enhancement of retention 24 hours later. This vasopressin effect was reversed by high doses of the vasopressor antagonist, dPtyr(Me) AVP. These results support the hypothesis that the visceral afferent signals may be involved in the apparent memory-enhancing effects of AVP, but the high doses of antagonist required suggest that factors other than a simple reversal of the pressor effects of AVP may be important.
Spatial learning and the hippocampal corticosterone receptor system of old rats: effect of the ACTH4-9 analogue ORG 2766.
Old (26 months) and young (6 months) male Wistar rats were treated chronically for 2 weeks with ORG 2766 or with vehicle, delivered via subcutaneously implanted minipumps (0.5 microgram peptide/0.5 microliter/h). Learning of a spatial task was not impaired in the old animals, except for one measure, i.e. the latency to find the goal box. In neither age group did ORG 2766 influence behavioral performance. The number of corticosterone receptor sites was decreased in the hippocampus of senescent rats, but restored to the level observed in young rats following ORG 2766 treatment. It is concluded that the number of hippocampal corticosterone receptor sites is a sensitive index of brain aging and effectiveness of ORG 2766.
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Facilitation of hot-plate response learning by pre- and posttraining naltrexone administration.
Retention performance for shock-motivated learning is generally enhanced by opiate antagonists. To test the hypothesis that opioid systems mediate learning and memory in nonshock-motivated tasks, the effects of naltrexone on hot-plate response learning were investigated. Naltrexone (0.1 or 1.0 mg/kg IP) 10 min before hot-plate exposure produced hyperalgesia, as measured by decreased latencies of naltrexone-injected mice to escape. Jump latencies, however, were not significantly decreased by naltrexone given 10 min before initial testing. Nevertheless, jump latencies of naltrexone-injected mice, but not saline-injected mice, decreased further on subsequent test trials 1 and 4 days later although treatment was discontinued, suggesting that the opiate antagonist also influenced learning or memory. Mice given naltrexone (0.3-10.0 mg/kg IP) immediately after their first hot-plate exposure also exhibited learning of the jump response, on a test trial 48 h later. The decreases in jump latencies on test trials were smaller after posttraining, than pretraining naltrexone administration. The results indicate that the effect of naltrexone on learning and memory can be at least partially separated from its hyperalgesic activity.
Pavlovian conditioning of drug-induced changes in body temperature.
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Learning and memory in young and aged Fischer 344 rats.
Changes in learning and memory processes that occur with senescence were investigated in male and female Fischer 344 rats, 3-26 mth of age. Age-related impairments were seen in retention of inhibitory avoidance learning, acquisition of a Y-maze discrimination task, and in a swim escape task with short intertrial training intervals. In contrast, old animals performed better than the young rats in an active avoidance task. No age differences were observed in either open field activity or in flinch or jump thresholds to footshock. These results indicate that impairments in learning and memory processes of aged rats are task-specific, and that memory deficits in old rats are best seen following one-time-only events or with weak training. The behavioral baselines described will help in the design of further research to correlate memory and neurobiological changes observed during the aging process in the rat.
Assessment of retention capacities in old rats.
Young (3-6 month) and old (24-27 month) barrier reared Wistar rats were tested for their ability to retain an inhibitory (passive) avoidance, acquired immobility, and a conditioned taste aversion response as a function of time. Old rats exhibited accelerated forgetting of both the inhibitory avoidance and acquired immobility response in comparison to young rats. In contrast, old rats displayed good retention of the conditioned taste aversion response at all time intervals tested. It appears that the dynamic aspects of retention are altered in aged rats depending on the task, and in some instances may be expressed as accelerated forgetting.
A mouse model of alcoholism.
A model of alcoholism should demonstrate self-administration of alcohol by the animal and a withdrawal syndrome when the animal no longer has access to the drug. A mouse model is described that meets these criteria and enables the induction of "alcoholism" in a large number of animals within a short period of time. Mice were injected daily with pyrazole, an inhibitor of alcohol dehydrogenase. The animals self-administered ethanol by inhaling vapour containing a relatively constant concentration of ethanol. Self-administration was voluntary: the mice could move to a chamber without ethanol vapour. During the first six days of each experiment, the animals were prompted to select the ethanol chamber by darkening that chamber. Most mice continued to self-administer ethanol without any prompting for at least 3 days; thereafter, preference for ethanol waned. Self-administration led to measurable levels of ethanol in blood and to the development of withdrawal when infusion of vapour was stopped.
Analysis of behavioural responses to an ACTH analog in CXB/By recombinant inbred mice.
Male mice of the C57BL/6By and BALB/cBy inbred strains, their reciprocal F1 hybrids, and 7 recombinant inbred strains, were tested for open-field activity, a shock-motivated successive reversal position discrimination problem in a T-maze, and a toggle box exploration task. The test battery was repeated one month later. Finally, mice were tested for the acquisition and extinction of a taste aversion conditioned by ethanol injection. Mice of each strain were tested after injection with saline or one of 3 doses of an ACTH analogue. Highly significant genotypic differences were found for all measures, an expected result. The strain distribution pattern seen in the toggle box suggested single gene mediation of exploratory activity after habituation. One aspect of avoidance responding and extinction of conditioned taste aversion also yielded strain distribution pattern consistent with single gene control. Peptide treatment reduced internal field crossings in the open field. This effect was not strain dependent. Peptide treatment had no effect on T-maze learning, conditioned taste aversion, or toggle-box exploration.
Enkephalin actions on avoidance conditioning may be related to adrenal medullary function.
The present series of studies was undertaken to better characterize the mechanisms mediating enkephalin actions on avoidance conditioning. Both Leu-and Met-enkephalin administered i.p. in amounts of 1.0 or 10.0 micrograms/kg 5 min before training in an active avoidance task significantly impaired acquisition of the response. Adrenal medullectomy, which removes an endogenous store of enkephalin-like peptides, abolished the effect on avoidance conditioning of 10.0 micrograms/kg of exogenously administered Met- or Leu-enkephalin. Increasing the dose of Leu-enkephalin by 10- or 100-fold restored its behavioral activity in adrenal demedullated rats. However, increasing (10-100-fold) or decreasing (10-fold) the dose of Met-enkephalin did not restore its activity in adrenal demedullated animals. This finding suggests that the impairing actions of the two enkephalins are not produced in the same way, but it is consistent with the interpretation that the adrenal medulla may play a role in mediating the actions of Met- and Leu-enkephalin on active avoidance conditioning.
Memory consolidation in senescence: effects of CO2, amphetamine and morphine.
Alterations in memory storage processes that occur in senescence were investigated by challenging young and old female "small Wistar" rats with posttraining administration of CO2, amphetamine or morphine, and measuring retention performance. Neither duration of CO2 immersion, nor the time of CO2 immersion after training had a differential amnestic effect with age on retention of a one-trial, shock-motivated inhibitory avoidance task. These results indicate that the times during which memory is susceptible to disruption for old and young rats are similar. Challenge with drugs, however, did reveal age-related alterations in memory storage processes. Amphetamine attenuated CO2-induced amnesia in young rats, but had no effect in old rats. This could not be attributed to a general decline in response to amphetamine in old rats because amphetamine increased open field activity of both young and old animals. Morphine also had a differential effect on memory with age: it caused amnesia in old rats trained in a one-trial hot plate escape task, while having no effect on retention performance of young rats. Thus, the modulatory influence of catecholamine and opioid systems on memory processes is probably altered in senescence.
Vasopressin and memory: the influence of prior experience with the training situation.
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Tolerance to ethanol hypothermia in inbred mice: genotypic correlations with behavioral responses.
Hypothermia was studied 5 min before, and 30 and 60 min after intraperitoneal administration of ethanol (3 g/kg) in 20 inbred strains of mice. Ethanol was given daily for 8 days, and temperatures were taken on Days 1, 3, 5, and 8. Tolerance was indexed by the reduction in hypothermia over days. There were large strain differences in baseline temperature, the hypothermic effect of ethanol, and in development of tolerance to hypothermia. Some strains of mice (DBA/1J, DBA/2N, MA/MyJ, and PL/J) did not develop tolerance to the hypothermic effect of ethanol. Initial sensitivity to the hypothermic effect of ethanol was significantly genetically correlated with tolerance development, indicating control of these responses by common genes. Ethanol-induced changes in activity and ataxia, as well as blood ethanol concentrations, were also assessed. Although there were significant strain differences in activity reduction, ataxia, blood-ethanol concentrations, and changes in these parameters during the course of chronic treatment, none of these variables could explain the genetic differences in hypothermic sensitivity and tolerance.
Ethanol preference in homozygous diabetes insipidus (Brattleboro) rats: effect of vasopressin fragments.
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Role of neurohormones as modulators of memory storage.
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Behavioral activity of met-enkephalin and ACTH4-10 and other peptides containing a phenylalanine and methionine residue.
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