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[Effects of systemic lidocaine, mepivacaine and bupivacaine on passive avoidance learning in mice].

The effects of local anesthetics on learning were assessed in mice through one trial step-through passive avoidance performance. Lidocaine HCl (10, 20 or 40 mg.kg-1), mepivacaine HCl (15, 30 or 60 mg.kg-1) or bupivacaine HCl (2.5, 5 or 10 mg.kg-1) were injected subcutaneously 10 min before acquisition training. Lidocaine, but not mepivacaine and bupivacaine, reduced the latency in the retention trial conducted 24hr after the training in a dose-dependent manner. However, lidocaine did not alter the latency when it was given 10 min before the retention trial. These results suggest that lidocaine impairs acquisition, but not retention or retrieval phase in the memory process.

Anesthetics, Local↗

Impairment of shock avoidance learning after long-term alcohol ingestion in mice.

Chronic alcohol consumption impaired the learning of a two-way shuttle box avoidance task in mice 10 to 14 days after the discontinuation of ethanol in the diet. Control groups received laboratory chow ad libitum or were pair-fed with the alcohol-consuming mice by diets containing isocaloric amounts of sucrose. The performance of the two control groups was indistinguishable from each other, and only the ethanol-consuming mice performed poorly. It was therefore concluded that alcohol consumption per se and not a nutritional deficiency was responsible for the impairment of learning.

Analysis of Variance↗

Involvement of GABAergic systems in benzodiazepine-induced impairment of passive avoidance learning in mice.

The possible involvement of GABAergic neuronal systems in benzodiazepine (BZP)-induced impairment of a passive avoidance response was investigated. Chlordiazepoxide (CDP) impaired passive avoidance when administered prior to training. The CDP-induced impairment was antagonized by pretreatment with picrotoxin, but not by pretreatment with bicuculline or post-training administration of picrotoxin. On the contrary, when combined with muscimol, the dose at which CDP impaired the response was lower than the dose at which it did so alone. The synergy of muscimol and CDP was attenuated by pretreatment with flumazenil or bicuculline. From these results, we conclude that GABAergic systems play an important role in the BZP-induced impairment of passive avoidance.

Animals↗

Dopamine D2L receptor knockout mice display deficits in positive and negative reinforcing properties of morphine and in avoidance learning.

The dopamine D2 receptor (D2) is implicated in drug addiction, learning and memory. Two isoforms of the D2 receptor, termed D2L (long form) and D2S (short form), have been identified. We previously generated mice lacking D2L (D2L-/-), but expressing functional D2S. In this study, we investigated the role of D2L in the positive and negative reinforcing properties of abused drugs and electrical stimuli, using D2L-/- mice as a model system. Mice were trained in three associative learning tasks: conditioned place preference to morphine and cocaine, conditioned place aversion to naloxone-precipitated morphine withdrawal, and active avoidance. D2L-/- mice, like wild type mice, developed a place preference to cocaine. In contrast to wild type mice, D2L-/- mice did not develop a place preference to morphine, nor did they attain a place aversion to morphine withdrawal. D2L-/- mice also failed to acquire avoidance behavior in response to electrical stimuli. There were no significant differences between D2L-/- and wild type mice in mu-opioid receptor density, morphine-induced locomotor stimulation and morphine withdrawal symptoms. These results suggest that D2L may have a greater impact than D2S on the rewarding aspects of morphine, and the aversive properties of morphine withdrawal and electrical stimulus. These findings also suggest that the presence of D2L is critical in the acquisition (learning) and/or retention (memory) of context-stimulus associations in certain situations. On the other hand, D2L is not essential for the rewarding aspects of cocaine and for the development of morphine dependence. Thus, these studies reveal distinct functional roles of D2L and/or D2S in drug addiction and avoidance learning, which may lead to a better understanding of the neurobiological basis underlying these behaviors.

Animals↗

Minaprine, but not oxiracetam, prevents desipramine-induced impairment of avoidance learning in mice.

The tricyclic antidepressant desipramine impaired shuttle-box avoidance acquisition in mice of the CD-1 strain. The nootropic drug oxiracetam was unable to prevent the desipramine-induced learning impairment, while a protective action was exerted by minaprine, a psychotropic agent regarded as an atypical antidepressant drug, possessing dopaminergic and related memory-enhancing properties. It seems likely that the dopaminergic action of minaprine played a determinant role in its avoidance improving effects in desipramine treated mice, because similar effects were produced by amphetamine. However, in contrast to amphetamine, minaprine did not enhance locomotor activity and did not show signs of general behavioral stimulation.

Animals↗

Noradrenaline and avoidance learning in the rat.

The selective neurotoxin 6-hydroxydopamine was used to deplete forebrain noradrenaline to less than 5% of control values and the learning capabilities of the depleted animals examined on a two-way active avoidance task. Noradrenaline depleted animals learned the two-way active avoidance task more quickly than controls and required fewer training trials to reach acquisition criterion. Twenty-four hour retention was not altered by the lesion, but significant resistance to extinction was seen when electric footshock was no longer presented. More detailed analysis of the improved acquisition shown by the lesioned animals revealed that the major effect lay in a reduced freezing response to footshock. This freezing tended to slow down learning in the control animals, since it was incompatible with the required two-way active avoidance response. No alteration was seen in sensory detection thresholds for electric footshock or in spontaneous locomotor activity in the absence of shock. These results are discussed in relation to theories of noradrenaline function in learning and memory and, more recently, in fear and anxiety.

Animals↗