Fear memory-induced alterations in the mRNA expression of G proteins in the mouse brain and the impact of immediate posttraining treatment with morphine.

Disturbances in fear-evoked signal transduction in the hippocampus (HP), the nuclei of the amygdala (AMY), and the prefrontal cortex (PFC) underlie anxiety-related disorders. However, the molecular mechanisms underlying these effects remain elusive. Heterotrimeric G proteins (GPs) are divided into the following four families based on the intracellular activity of their alpha subunit (Gα): Gα(s) proteins stimulate cyclic AMP (cAMP) generation, Gα(i/o) proteins inhibit the cAMP pathway, Gα(q/11) proteins increase the intracellular Ca concentration and the inositol trisphosphate level, and Gα(12/13) proteins activate monomeric GP-Rho.

Early maternal separation: a rodent model of depression and a prevailing human condition.

The early life of most mammals is spent in close contact with the mother, and for the neonate, early maternal separation is a traumatic event that, depending on various conditions, may shape its behavioral and neurochemical phenotype in adulthood. Studies on rodents demonstrated that a very brief separation followed by increased maternal care may positively affect the development of the offspring but that prolonged separation causes significant amounts of stress. The consequences of this stress (particularly the hyperreactivity of the HPA (hypothalamic-pituitary-adrenal) axis are expressed in adulthood and persist for life.

Brief maternal separation affects brain α1-adrenoceptors and apoptotic signaling in adult mice.

Exposure to adversity during early life is a risk factor for the development of different mood and psychiatric disorders, including depressive-like behaviors. Here, neonatal mice were temporarily but repeatedly (day 1 to day 13) separated from mothers and placed in a testing environment containing a layer of odorless clean bedding (CB). We assessed in adult animals the impact of this early experience on binding sites and mRNA expression of α1-adrenergic receptor subtypes, heat shock proteins (HSPs) and proapoptotic and antiapoptotic members of the Bcl-2 family proteins in different brain regions involved in processing of olfactory information and rewarding stimuli.

[Neurochemistry of impulsiveness and aggression].

Aggression is the most frequent social reaction among animals and men, and plays an important role in survival of the fittest. The change of social conditions in the course of development of human civilisation rendered some forms of aggression counter-adaptive, but the neurobiological mechanism of expression of aggression have not fundamentally changed in the last stages of human evolution. The two different kinds of aggression: emotional, serving mainly as a threat, and rational, predatory, serving for the attainment of goal in the most effective way, have different anatomical and neurobiological background and reciprocally inhibit each other.

Morphine-induced place preference affects mRNA expression of G protein α subunits in rat brain.

Background: The conditioned place preference (CPP) test is an animal model serving to assess addictive potential of drugs in which environmental cues become associated with the subjective effects of drugs of abuse. Morphine, a known addictive drug, is an agonist of opioid receptors that couple to the G(i/o) family of guanine nucleotide-binding proteins (GP). We have recently found that chronic treatment with morphine affects mRNA levels of GPs that are not coupled to opioid receptors (OR).

Changes induced by formalin pain in central alpha1-adrenoceptor density are modulated by adenosine receptor agonists.

We aimed to elucidate the role of alpha(1)-adrenoceptors in adenosine analgesia in the formalin test. Formalin was injected into the hind paw of male CD-1 mice after injection of adenosine A(1) or A(2a) receptor agonists, CPA, [N(6)-cyclopentyladenosine], and CGS21680 [2-p-(2-carboxyethyl)-phenylethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride]. In the behavioral experiment, alpha(1)-adrenoceptors were blocked by an alpha(1)-adrenoceptor antagonist prazosin, 0.

Paroxetine pretreatment does not change the effects induced in the rat cortical beta-adrenergic receptor system by repetitive transcranial magnetic stimulation and electroconvulsive shock.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a clinically effective antidepressant treatment, but meta-analysis suggests that its efficacy is marginal. We investigated whether the administration of rTMS together with paroxetine would enhance its effects on the beta-adrenergic system of the rat. We compared our results with the effects of electroconvulsive shock therapy (ECS).

3-Methoxytyramine, an extraneuronal dopamine metabolite plays a physiological role in the brain as an inhibitory regulator of catecholaminergic activity.

3-Methoxytyramine (3-MT), an extraneuronal metabolite of dopamine, present in the synaptic cleft at a very low amount (low nanomolar range), comparable to dopamine concentration, is generally regarded as a biologically inactive compound. We have shown in this study that 3-MT binds to the rat noradrenergic cortical alpha(1) and striatal dopamine D(1) and D(2) receptors in nanomolar concentration range, and to cortical alpha(2) adrenoceptor at low micromolar concentration. Bilateral intrastriatal injections of 3-MT (0.

Does the presence of morphine counteract adaptive changes in expression of G-protein alpha subunits mRNA induced by chronic morphine treatment?

Opiate dependence develops due to changes in intracellular signaling caused by long-term exposure to morphine. Here we investigated changes in the mRNA expression of the main classes of G-protein alpha (Galpha) subunits in various brain regions in morphine-dependent rats. Rats received increasing doses of morphine, 10-50 mg/kg, b.

Diverse effects of GABA-mimetic drugs on cocaine-evoked self-administration and discriminative stimulus effects in rats.

Rationale: Recent data indicate that gamma-aminobutyric acid (GABA) is a modulator of behavioral responses to cocaine.

Objective: The efficacy of gabapentin (a cyclic GABA analogue), tiagabine (a GABA reuptake inhibitor), or vigabatrin (an inhibitor of GABA transaminase and reuptake) to alter cocaine-seeking behavior and discriminative effects was examined in rats.

Materials And Methods: Rats were trained to press a lever for cocaine (0.

Nicotine potentiates imipramine-induced effects on catecholamine metabolism: possible relation to antidepressant activity.

Following our behavioral studies demonstrating augmentation of imipramine action by concomitant administration of nicotine, we investigated the effects of one or 14 days of treatment (twice daily) with imipramine and nicotine on dopamine metabolism in various brain areas of rat and noradrenaline in the brain stem. In addition, we evaluated the responses of this metabolism to apomorphine challenge in the rat. Generally, chronic treatment of imipramine and nicotine produced opposite effects to acute administration.

Effect of cocaine sensitization on alpha1-adrenoceptors in brain regions of the rat: an autoradiographic analysis.

We investigated the effects of repeated intermittent cocaine treatment, resulting in behavioral sensitization, on the density of alpha(1)-adrenoceptors in the rat brain measured by quantitative in vitro autoradiography of [(3)H]prazosin. Animals were decapitated following a short (2 h) and long (48 h) withdrawal period after an injection of cocaine (10 mg/kg) on day 10 given to either cocaine-naive (saline daily, days 1-5) or cocaine-sensitized (cocaine 10 mg/kg daily, days 1-5) rats. In cocaine-naive rats, significant decreases in alpha(1)-adrenoceptors 2 h after a single dose of cocaine were observed in the amygdaloid nuclei and hippocampus; the decreases in the centromedial nucleus of the amygdala persisted until 48th hour of withdrawal.

Various GABA-mimetic drugs differently affect cocaine-evoked hyperlocomotion and sensitization.

To substantiate the notion that cocaine behavioral effects may be influenced by gamma-aminobutyric acid (GABA) neurotransmission male Wistar rats were injected with gabapentin (a cyclic GABA analogue), tiagabine (a GABA reuptake inhibitor), or vigabatrin (a GABA transaminase inhibitor) before acute or repeated treatment with cocaine evoking either locomotor hyperactivation or sensitization. Gabapentin (1-30 mg/kg), tiagabine (2.5-10 mg/kg) or vigabatrin (75-250 mg/kg) attenuated the cocaine (10 mg/kg)-induced hyperactivation and in the highest doses they also decreased basal locomotor activation.

The mechanism of 1,2,3,4-tetrahydroisoquinolines neuroprotection: the importance of free radicals scavenging properties and inhibition of glutamate-induced excitotoxicity.

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), unlike several other tetrahydroisoquinolines, displays neuroprotective properties. To elucidate this action we compared the effects of 1MeTIQ with 1,2,3,4-tetrahydroisoquinoline (TIQ), a compound sharing many activities with 1MeTIQ (among them reducing free radicals formed during dopamine catabolism), but offering no clear neuroprotection. We found that the compounds similarly inhibit free-radical generation in an abiotic system, as well as indices of neurotoxicity (caspase-3 activity and lactate dehydrogenase release) induced by glutamate in mouse embryonic primary cell cultures (a preparation resistant to NMDA toxicity).

Conditioned rewarding stimulus associated with cocaine self-administration reverses the depression of catecholamine brain systems following cocaine withdrawal in rats.

Craving phenomena are related to induction of substance-seeking behaviour by stimuli associated with the availability of the drug. We investigated the changes in monoamine metabolism in regions of the brains of rats that, following a period of training of cocaine self-administration, were either killed 2 h after the last session or underwent extinction trials, during which cocaine was withdrawn. During the training, acoustic and visual stimuli announced the availability of cocaine.

Nicotine produces antidepressant-like actions: Behavioral and neurochemical evidence.

Converging lines of evidence indicate the involvement of nicotinic acetylcholine receptors in depressive illness and antidepressant drug action. We investigated the effects of sub-chronic and chronic treatment with imipramine, nicotine and their combination on: (a) the ability of a dopamine-mimetic challenge to produce locomotor stimulation and (b) cortical density of beta-adrenoceptors. One week of treatment with imipramine (10 mg/kg, twice daily) did not result in an altered response to the apomorphine (0.

Carane derivative stereoisomers of different local anaesthetic and antiplatelet activity similarly potentiate forskolin-stimulated cyclic AMP response and bind to beta-adrenoceptors in the rat brain cortex.

A carane derivative, KP-23 [RS](-)-4-(2-hydroxy-3)N-isopropylamino)-propoxyimino)-cis-carane, was earlier described as a potential local anaesthetic and antiplatelet agent, and the following studies revealed that its R and S stereoisomers, KP-23R and KP-23S, have different potencies in the infiltration anaesthesia and platelet aggregation tests. The effects of these stereoisomers on the cyclic AMP (cAMP) generating system and the displacement of [(3)H]CGP 12177 (a beta-adrenoceptor ligand) from its binding sites in the rat cerebral cortical tissue were investigated. The stereoisomers did not affect the basal cAMP level, but, at concentrations between 10(-4) and 10(-3) M, they elevated the forskolin-induced accumulation of cAMP with similar potency.

Protective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline against dopaminergic neurodegeneration in the extrapyramidal structures produced by intracerebral injection of rotenone.

The aim of this paper was to investigate whether rotenone, a pesticide causing experimental parkinsonism, causes direct damage to dopaminergic structure when injected intracerebrally and whether this action may be prevented by peripheral administration of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), an endogenous compound with anti-dopaminergic activity. Male Wistar rats were injected unilaterally into the median forebrain bundle with 2 microg rotenone, and received 1MeTIQ, 50 mg/kg i.p.

Effect of combined treatment with paroxetine and transcranial magnetic stimulation (TMS) on the mitogen-induced proliferative response of rat lymphocytes.

Depression is associated with abnormal functions of the immune system. In this study, we investigated how two modem antidepressant therapies, chronic treatment with transcranial magnetic stimulation (TMS) and administration of an antidepressant belonging to selective serotonin reuptake inhibitors (SSRI), paroxetine, affect the proliferative response of thymocytes and splenocytes stimulated in vitro with various mitogens. Paroxetine (10 mg/kg) and TMS (B = 1.

A possible physiological role for cerebral tetrahydroisoquinolines.

Tetrahydroisoquinolines present in the mammalian brain, 1,2,3,4-tetrahydroisoquinoline (TIQ) and salsolinol, suspected to cause neurodegeneration leading to Parkinson's disease, were investigated to find their possible physiological role. To this aim their behavioral and receptor effects induced after a single dose were tested in mice and rats. Both compounds do not affect significantly the basal locomotor activity, very effectively block hyperactivity induced by apomorphine (rats) and amphetamine (mice), only partially block hyperactivity induced by scopolamine, do not affect locomotor stimulation induced by cocaine, and strongly augment the running fit induced by morphine (mice).

1-methyl-1,2,3,4-tetrahydroisoquinoline protects against rotenone-induced mortality and biochemical changes in rat brain.

The effect of single and multiple administration of the neurotoxic pesticide, rotenone, and the potentially neuroprotective compound, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), on the concentration of dopamine and its metabolites (homovanillic acid-HVA, 3,4-dihydroxyphenylacetic acid-DOPAC, and 3-methoxytyramine-3-MT)) in three brain areas was studied by high-performance liquid chromatography (HPLC) with electrochemical detection in Wistar rats. The rate of dopamine catabolism in the striatum along the N-oxidative and O-methylation pathways was assessed by calculation of the ratio of dopamine metabolites to dopamine. In addition, the effect of rotenone on mortality and general behavior of rats was investigated.

Repeated imipramine and electroconvulsive shock increase alpha 1A-adrenoceptor mRNA level in rat prefrontal cortex.

alpha(1)-Adrenoceptors have been implicated in the mechanism of action of antidepressants, but their action on specific receptor subtypes was rarely reported. We compared now the action of two prototypic antidepressant treatments: repeated imipramine and electroconvulsive shock, on the expression of the alpha(1A)- and alpha(1B)-adrenoceptor mRNAs and on the receptor density in rats. The mRNA expression was assessed by Northern blot in the prefrontal cortex and the hippocampus, the receptor density was measured by [3H]prazosin binding in the total cerebral cortex and hippocampus.

The influence of rapid-rate transcranial magnetic stimulation (rTMS) parameters on rTMS effects in Porsolt's forced swimming test.

To assess the similarity of the behavioural effects of the rapid transcranial magnetic stimulation (rTMS) to those produced by other antidepressant treatments, in particular to repeated electroconvulsive shock (ECS), we carried out experiments on Wistar rats. The effects of a standard ECS procedure (9 daily treatments; the current parameters: 150 mA, 50 Hz, 0.5 s) were compared with 18 d treatment with rTMS of the same field intensity of 1.