Passive Avoidance Behavior In Mice Research Articles

Facilitation of avoidance behaviour in mice chronically treated with heroin or methadone

Although the repercussion of chronic treatment with large amounts of opioids on cognitive performance is a matter of concern, the effects of opioid drugs on passive avoidance learning have been scarcely studied. Here, we analyzed the effects of prolonged administration of heroin and methadone, as well as the impact of suffering repeated episodes of withdrawal on fear-motivated learning using the passive avoidance test. Mice received chronic treatment (39 days) with methadone (10mg/kg/24h), associated or not with repeated withdrawal episodes, or with heroin (5mg/kg/12h). Our results show that, regardless of the type of treatment received, all mice displayed similar basal thermal nociceptive thresholds during 25 days of treatment. In the hot plate test, both methadone and heroin induced antinociception 30min after drug administration. The analgesic effect was absent when measured 4h after heroin and 12h after methadone. Pain behavioural responses elicited by growing intensities of electric shock, applied on day 28th of treatment, were similar in all groups of mice. Our results indicate that chronic opioid treatment had promnesic effects on passive avoidance behaviour in mice, unrelated to changes in the nociceptive state.

Effects of an aqueous extract of Puerariae flos (Thomsonide) on impairment of passive avoidance behavior in mice

The effects of an aqueous extract of Puerariae flos (Thomsonide) on ethanol-induced learning and memory impairment and scopolamine-induced amnesia were investigated. Thomsonide exerted an ameliorating effect on the impairment of both memory registration and memory retrieval induced by ethanol. These results indicate that Thomsonide has an antiamnesic effect on the central nervous system in alcoholic intoxication and support the traditional use of Puerariae flos for the treatment of alcoholic intoxication. Thomsonide also improved the scopolamine-induced impairment of memory registration in passive avoidance behavior in mice. The results of this study suggest that it may be possible to use Thomsonide for the treatment of age-related memory impairment and dementia.

Specific cholinergic destruction in the basal magnocellular necleus and impaired passive avoidance behavior of rodents

A nerve growth factor (NGF)-diphtheria toxin conjugate (NGDT) was found to selectively abolish or depress the activity of NGF receptor-bearing cholinergic neurons of the basal magnocellular nucleus (BMN). Bilateral cortical injections of NGDT impaired the retention of passive avoidance behavior in mice. A memory deficit was also revealed when cortical injections of NGDT were administered after the acquisition of a passive avoidance response. Thus, retrograde destruction of BMN cholinergic neurons by the cortical injection of NGDT interfered with both learning and memory processes. The animal model outlined here should be useful in analyzing the pathogenesis of Alzheimer's disease and the functions of the cholinergic system in the BMN.

Effects of vinburnine on experimental models of learning and memory impairments

Retrograde amnesia can be induced experimentally in mice injecting them with scopolamine (3 mg/kg, IP) or by inducing seizures with pentylenetetrazol (50 mg/kg, IP), and in rats by subjecting them to hypobaric hypoxia (at a barometric pressure of 300 mmHg for 3 min). We have studied the effects of vinburnine (VNB) in these amnesic states compared to vincamine (VNC) and nicergoline (NCG), in order to assess its activity on drug-induced learning and memory impairments. Vinburnine reduced the disrupting effect of both scopolamine and pentylenetetrazol-induced seizures on the retention of a step-through passive avoidance behavior in mice and on the acquisition of shuttle-box active avoidance behavior in rats. This effect was dose-related up to 20 mg/kg, the peak effect dose after IP administration, and more pronounced than that of VNC and NCG in some tests. These results indicate that VNB influences learning and memory processes disrupted by a pharmacological manipulation. In particular, as scopolamine acts as anticholinergic drug, it is possible that VNB mechanism of action includes also a stimulation of acetylcholine neurotransmission.

Changes in plasma corticosterone and cerebral biogenic amines and their catabolites during training and testing of mice in passive avoidance behavior

Concentrations of cerebral biogenic amines and their catabolites, and of plasma corticosterone were determined 10 min after training and testing of passive avoidance behavior in mice. Training and testing of mice that had acquired the task well resulted in statistically significant increases of plasma corticosterone, of the DOPAC:DA ratio [an index of dopamine (DA) metabolism] in prefrontal cortex, and of MHPG:NE ratios [an index of norepinephrine (NE) metabolism] in hypothalamus and brain stem. There were also decreases of NE in hypothalamus and brain stem, and an increase of 5-HIAA:5-HT [an index of serotonin (5-HT) metabolism] and of tryptophan in brain stem. Some of these changes also occurred in mice merely exposed to the apparatus but not trained. Plasma corticosterone concentrations were significantly higher in mice that performed the task well compared to those that did not, and there were significant correlations between this measure and the avoidance performance. Although there was only one statistically significant correlation between a cerebral metabolite and the avoidance performance (a decrease in hypothalamic NE), there were indications of relationships between cerebral biogenic amine metabolism and the performance. The patterns of neurochemical and endocrine changes closely resemble those previously observed in response to various stressors. Thus, the changes could reflect stress responses, which may or may not be related directly to the performance of the avoidance task.

Effects of flunitrazepam on passive avoidance behaviour in mice subjected to immobilization stress or familiarized with the testing apparatus

The effects of flunitrazepam on passive avoidance behaviour were investigated in DBA/2 mice. In a first set of experiments retention performance impairment was observed in mice injected with the drug immediately but not 120 min after training. In a second set of experiments, immobilization stress enhanced, while familiarization with the apparatus decreased, the effects of flunitrazepam, suggesting involvement of emotional factors. All the effects observed were antagonized by naltrexone, showing involvement of opioid receptors.

Dose- and strain-dependent effects of dermorphin and [D-Ala–2-D-Leu–5]enkephalin on passive avoidance behavior in mice.

Dose- and strain-dependent effects of dermorphin and [D-Ala–2-D-Leu–5]enkephalin on passive avoidance behavior in mice.

Dose- and strain-dependent effects of dermorphin and [D-Ala-2-D-Leu-5]enkephalin on passive avoidance behavior in mice.

Dermorphin and [D-Ala2-D-Leu5]enkephalin, administered intracerebroventricularly (icv) immediately after training in a passive avoidance test, exerted dose- and strain-dependent effects in DBA/2 (DBA) and C57BL/6 (C57) mice. In fact, the peptides impaired, at a low dose (5 ng), the retention performances of both strains; a higher dose (50 ng) impaired retention in DBA but improved it in C57 mice. A dose of naloxone (0.3 microgram, icv), which was ineffective when administered alone, antagonized the effects observed. The results are discussed in terms of strain differences in central mechanisms.

Naltrexone-reversible effects of flunitrazepam on locomotor activity and passive avoidance behaviour in mice

Some behavioural effects of flunitrazepam were investigated in two sets of experiment in C57BL/6 mice. In the first set, funitrazepam administration (0.025 or 0.05 mg/kg) enhanced the locomotor activity of mice. In the second set, memory impairments were observed following posttraining (immediately or 30 min, but not 60 min) treatment with the drug (0.05 mg/kg). All effects were antagonized by a per ineffective dose of naltrexone (0.5 mg/kg for the activity, 0.1 mg/kg for the memory experiments), suggesting the involvement of opioid receptors. The results are discussed on the basis of recent evidence suggesting a link between benzodiazepine and opiate mechanisms of action.

Naloxone-reversible effects of ethanol on passive avoidance behavior in mice

Performance impairments were evident, in CD1 mice tested in a passive avoidance apparatus, following posttrial intraperitoneal administration of ethanol (1.0 and 2.0 g/kg) or morphine (0.5 and 1.0 mg/kg), or following posttrial immobilization stress (30 and 60 min). Lower doses of ethanol (0.5 g/kg) or morphine (0.25 mg/kg), or a shorter immobilization time (15 min) were ineffective. Ethanol, at an ineffective dose (0.50 g/kg) enhanced both the effects of morphine and those of immobilization stress. The effects observed were antagonized by a per se ineffective dose of naloxone (1.0 mg/kg). The possibility that opiates may have a critical but modulatory effect on the actions of ethanol and/or immobilization is discussed.

Effects of N-hydroxyethyl-pyrrolidinium methiodide, a choline analogue, on passive avoidance behaviour in mice

N-Hydroxyethyl-pyrrolidinium methiodide (pyrrolcholine) administered intraventricularly impaired passive avoidance learning in mice. This effect of pyrrolcholine was antagonized by choline and hemicholinium-3, potentiated by scopolamine, and depending upon the time of injection, either potentiated or antagonized by physostigmine. The results are consistent with the hypothesis that pyrrolcholine disrupts central cholinergic pathways by a presynaptic mechanism. Based on metabolism studies, both in vitro and in vivo, it is postulated that the action of pyrrolcholine is mediated via acetylpyrrolcholine, a putative cholinergic false transmitter