Effects of Activation and Blockade of Dopamine Receptors on the Extinction of a Passive Avoidance Reaction in Mice with a Depressive-Like State

Learning and extinction of a conditioned passive avoidance reaction resulting from neuropharmacological actions on dopamine D₁ and D₂ receptors were demonstrated to be specific in intact mice and in mice with a depressive-like state. Learning was degraded only after administration of the D₂ receptor antagonist sulpiride and was independent of the initial functional state of the mice. In intact mice, activation of D₂ receptors with quinpirole led to a deficit of extinction, consisting of a reduction in the ability to acquire new inhibitory learning in conditions associated with the disappearance of the expected punishment. In mice with the “behavioral despair” reaction, characterized by delayed extinction, activation of D₁ receptors with SKF38393 normalized this process, while the D₂ agonist was ineffective. A positive effect consisting of accelerated extinction of the memory of fear of the dark (“dangerous”) sector of the experimental chamber was also seen on blockade of both types of dopamine receptor.     

Effects of Acute Stress in Mice with 5-HT1A Receptors with Different Sensitivities to Chronic Activation by 8-OH-DPAT

Neuroscience and Behavioral Physiology - Recombinant mouse strain B6.CBA-D13Mit76C (B6-M76C) and B6.CBA-D13Mit76B (B6-M76B), with 5-HT1A receptors with different sensitivities to chronic activation...     

Studies of the Interaction between Behavioral Stereotypes and the Effects of Activation of Presynaptic Dopamine Receptors during Extinction and Amnesia in Mice

The involvement of presynaptic dopamine receptors in the retention of a conditioned passive avoidance reflex through extinction and amnesia was studied in C57BL/6J mice selected in a 20-day aggressive conflict test for aggressive and submissive behavioral stereotypes. These experiments showed that in aggressive mice, activation of presynaptic receptors with the agonist (+)3-(3-hydroxyphenyl)-N-n-propylpiperidine [(+)3PPP] at a dose of 2 mg/kg degraded learning, significantly decreased the retention time of the acquired conditioned habit in extinction, and increased the effect of an amnesia-inducing treatment. Mice showing submissive behavior in daily confrontations with aggressors responded to administration of (+)3PPP with long-lasting reproduction of the conditioned passive avoidance reaction during extinction and showed no changes in the development of amnesia. These data on the relationship between the effects of activating presynaptic dopamine receptors in reproduction of the memory trace in conditions of trace disruption on the one hand and behavioral status on the other are assessed from the point of view of different basal levels of dopaminergic system operation in aggressive and submissive mice.     

The Effects of Activation and Blockade of Central P2X Receptors on Body Temperature

The aim of the present work was to identify the role of ATP acting on specific P2X receptors in the central mechanisms of thermoregulation. Immunohistochemical studies demonstrated that brainstem structures involved in controlling body temperature contained large number of nerve cells bearing P2X ATP receptors. Experiments on conscious rats involving intracerebroventricular administration of an ATP analog and P2X antagonists showed that both activation and blockade of central P2X receptors produced marked changes in body temperature. Analysis of the effects of these substances provided grounds for suggesting that ATP acting on P2X receptors fulfils an important function in the mechanisms of transmitting afferent information from peripheral thermal receptors to thermoregulatory centers in the brainstem with responsibility for heat loss, while in pyrogen-induced fever ATP acting on these receptors may be involved in the activity of the endogenous antipyretic system.     

Operant Behavior in Conditions of Activation and Blockade of Neostriatal Muscarinic Receptors

Chronic experiments were performed on four dogs using a model of an operant defensive reflex associated with maintaining a flexion posture to study the effects of bilateral intraneostriatal microinjection of the non-selective muscarinic receptor agonist carbachol, the selective D2 dopamine receptor blocker raclopride, and the selective M1 muscarinic receptor blocker pirenzipine on the performance of the operant defensive reflex and differentiation of signals. The results show that microinjection of carbachol induced increases in the tonic component and inhibition of the phasic component of the reflex, an ordering rearrangement of the posture, and increases in the amplitudes of its components. Raclopride microinjection gave similar but less marked results. The greatest effects with both substances were seen using differential stimuli. There were sharp increases in the process of differentiation of sound signals. Pirenzipine microinjections gave the opposite result. These data are assessed on the basis of concepts of the existence of two efferent outputs from the neostriatum with opposite effects on their targets and the roles of muscarinic and dopamine receptors in triggering and blocking these effects.     

Blockade of D1 Dopamine Receptors in the Cat Motor Cortex Induces Increases in the Latent Period of a Conditioned Forepaw Support-Placing Reflex

Neuroscience and Behavioral Physiology -     

Comparison of Changes in Glutamate Levels in the Nucleus Accumbens of the Rat Brain during Food Consumption in Conditions of Blockade of Dopamine D1 and D2 Receptors

The effects of blockade of D₁ and D₂ dopamine receptors in the nucleus accumbens on changes in glutamate levels in the intercellular space of this structure during food consumption were studied in Sprague–Dawley rats by intracerebral microdialysis combined with HPLC. These experiments showed that food consumption was accompanied by decreases in glutamate levels in the intercellular spaces of the nucleus accumbens. Blockade of D₁ dopamine receptors with SCH-23390 (0.01 mM) produced no changes in the dynamics of glutamate release during food consumption. Food consumption in conditions of blockade of D₂ dopamine receptors with raclopride (0.01 mM) induced increases in glutamate levels. These data suggest that glutamate levels during food consumption are controlled by the dopaminergic system of the nucleus accumbens, mediated by D₂ but not D₁ dopamine receptors.     

Structural Characteristics of Ionotropic Glutamate Receptors as Identified by Channel Blockade

The channels of four types of ionotropic glutamate receptor (NMDA receptors and Ca-permeable AMPA receptors of rat brain neurons, and cation-selective receptors from mollusk neurons and insect postsynaptic muscle membranes) and two subtypes of nicotinic cholinoreceptor (from frog neuromuscular junctions and cat sympathetic ganglia) were studied. The structural characteristics of channels determining their susceptibility to blockade by organic mono- and dications were identified. These studies used homologous series of adamantane and phenylcyclohexyl derivatives. These experiments showed that the receptors studied here could be divided into two groups. The first group included the AMPA receptor and the mollusk and insect receptors. These were characterized by the lack of effect on the part of monocations and a strong relationship between the activity of dications and the distance between nitrogen atoms. The second group included the NMDA receptor and both subtypes of the nicotinic cholinoreceptor (muscular and neuronal). Here, conversely, the activity of monocations and dications, regardless of their lengths, were essentially identical. A model for the binding sites of blockers in channels is proposed, which takes these observations into account.     

The Effects of Beta-Adrenergic Stimulation and Beta-Adrenergic Blockade on Emotional Reactions

In order to examine the effects of beta-adrenergic arousal on emotional reactions, 84 male students received either 40 mg of the beta-adrenergic blocking agent oxprenolol, placebo, or 20 mg of the beta-stimulating agent orciprenaline. They were placed in one of two situations designed to induce either angerlike or no emotional reactions (neutral control). Dependent variables were heart rate, blood pressure, galvanic skin response, and self reports of bodily and emotional state. The drugs as well as the “anger situation” influenced bodily changes. Reports of anger were increased only under the placebo condition. Under oxprenolol the “anger situation” had no effects on reported emotions, whereas under orciprenaline the “anger situation” led to an increase in reports of anxiety. Characteristics of the “anger situation” and of the sympathetic response pattern induced by orciprenaline are discussed as possible explanations for the latter result.     

Pulmonary Microcirculation during Experimental Pulmonary Thromboembolism under Conditions of Activation and Blockade of Muscarinic Acetylcholine Receptors

Bulletin of Experimental Biology and Medicine - Changes in pulmonary microcirculation were studied in isolated perfused rabbit lungs during modelling pulmonary thromboembolism under conditions of...     

No Association Between Polymorphisms in the Human Dopamine D3 and D4 Receptors Genes and Alcoholism

The human dopamine D₂ receptor gene (DRD₂) has received considerable attention for the past several years as a potential candidate that may affect susceptibility to alcoholism. The association studies that compared the frequencies of alleles of DRD₂ gene between alcoholics and control groups have produced equivocal results. Dopamine D₃ and D₄ receptor genes (DRD₃ and DRD₄) are in the same class as DRD₂ but with different pharmacological properties. We have used relative risk and haplotype relative risk approaches to test associations between alleles of DRD₃ and DRD₄ genes and alcoholism. For relative risk studies 162 probands from multiple incidence alcoholic families have been compared to 89 psychiatrically normal controls. Haplotype relative risk approaches have used 29 alcoholic probands in which both parents were available for genotyping. The Bal I restriction enzyme site in DRD₃ and tandem repeat (VNTR) in DRD₄ genes polymorphisms were used to genotype the above samples. The results of relative risk approaches for both DRD₃ and DRD₄ genes were negative for comparisons of alcoholics and subtypes of alcoholics with normal controls. Haplotype relative risk approaches also were negative for both genes. These results suggest that any role played by these receptors may account for only part of the variation in susceptibility to alcoholism. Am. J. Med. Genet. 74:281–285, 1997. © 1997 Wiley-Liss, Inc.