Repeated moderate-dose ethanol bouts impair cognitive function in Wistar rats.

The effects of repeated, intermittent administration of a moderate dose of ethanol (3.4 g/kg/day × 6 days, intragastrically via gavages) on cognitive function were examined in male Wistar rats. No significant differences in weight gain between the ethanol- and water-treated rats were found.

Enhanced cerebral expression of MCT1 and MCT2 in a rat ischemia model occurs in activated microglial cells.

Monocarboxylate transporters (MCTs) are essential for the use of lactate, an energy substrate known to be overproduced in brain during an ischemic episode. The expression of MCT1 and MCT2 was investigated at 48 h of reperfusion from focal ischemia induced by unilateral extradural compression in Wistar rats. Increased MCT1 mRNA expression was detected in the injured cortex and hippocampus of compressed animals compared to sham controls.

Secondary brain injuries in thalamus and hippocampus after focal ischemia caused by mild, transient extradural compression of the somatosensori cortex in the rat.

The development and distribution of secondary brain lesions, subsequent to ischemic stroke, are of considerable clinical interest but so far only a limited number of studies have investigated the distribution and development of these secondary lesions in detail. In this study, we used an animal model of focal ischemia caused by extradural compression of the sensorimotor cortex. This paradigm of focal ischemia was shown to produce a consistent pattern of secondary lesions located distally from the primary lesion.

Effects of subunit selective nACh receptors on operant ethanol self-administration and relapse-like ethanol-drinking behavior.

Rationale And Objectives: The sensitivity to ethanol central effects is partially determined by the subunit composition of brain nicotinic acetylcholine receptors (nAChRs). Thus, the effects of intraventral tegmental area (VTA) administration of the nicotinic subunit-specific antagonist, alpha-conotoxin MII (alphaCtxMII, alpha(3)beta(2)*, beta(3)*, alpha(6)*), were compared to those of systemic mecamylamine (MEC, an allosteric negative modulator of the nAChR), dihydro-beta-erythroidine (DHbetaE, alpha(4)beta(2)*), and methyllycaconitine (MLA, alpha(7)*) to elucidate involvement of different subunits of nAChRs in operant ethanol self-administration and relapse-like activation of ethanol consumption after ethanol deprivation in rats.

Methods: The effects of drugs were studied in rats trained for operant oral self-administration of ethanol (FR = 1).

Memantine enhances the inhibitory effects of naltrexone on ethanol consumption.

Effects of the opioid receptor antagonist naltrexone (0.1; 0.3; 1.

The role of hypothalamic peptide gene expression in alcohol self-administration behavior.

Self-administration of ethanol and food share many common features and Richter hypothesized that an increase in ethanol consumption would decrease feeding to balance the excess calories contained in the ethanol. Previously, we have shown that individual alcohol consumption correlates with neurotransmitter gene expression, especially in the prefrontal cortex. To test the hypothesis of Richter, we measured hypothalamic gene expression of receptors or neuropeptides of known relevance for the regulation of food intake using qPCR and correlated this to individual ethanol consumption in Wistar rats.

Diabetic type II Goto-Kakizaki rats show progressively decreasing exploratory activity and learning impairments in fixed and progressive ratios of a lever-press task.

Learning and memory impairments associated with diabetes have been reproduced in rodent models of diabetes type I, but few studies have been performed in spontaneously type II diabetic rodents. The study of type II diabetic rats such as the Goto-Kakizaki (GK) rat is of advantage when characterizing the development of cognitive impairments specifically caused by the progression of the disease and not by its treatment. We thus hypothesized that GK rats might display learning impairments when compared to non-diabetic Wistar rats.

Reduced HO-1 protein expression is associated with more severe neurodegeneration after transient ischemia induced by cortical compression in diabetic Goto-Kakizaki rats.

Pronounced hyperglycemia provoked by extradural compression (EC) of the sensorimotor cortex was recently described in the non-insulin dependent Goto-Kakizaki (GK) diabetic rat. Compared with control Wistar rats, GK rats exhibited more extensive brain damage after cortical ischemia at 48 h of reperfusion (Moreira et al, 2007). We hypothesized that the enhanced brain injury in GK rats could be caused by differential regulation of the heme degrading enzyme heme oxygenase (HO)-1, known to interact with the expression of other target genes implicated in antioxidant defense, inflammation and neurodegeneration, such as superoxide dismutase (SOD)-1, -2, inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNFalpha).

Delayed access to alcohol accelerates self-administration of alcohol on a progressive ratio schedule.

In a previous report, we found that a 5-min. delay in alcohol access increases ethanol intake in rats trained to self-administer 5% ethanol. To assess the effects of this delay on the motivation to self-administer ethanol, Wistar rats were trained on a progressive ratio schedule of reinforcement and presented with the 5-min.

Diabetic Goto-Kakizaki rats display pronounced hyperglycemia and longer-lasting cognitive impairments following ischemia induced by cortical compression.

Hyperglycemia has been shown to worsen the outcome of brain ischemia in several animal models but few experimental studies have investigated impairments in cognition induced by ischemic brain lesions in hyperglycemic animals. The Goto-Kakizaki (GK) rat naturally develops type 2 diabetes characterized by mild hyperglycemia and insulin resistance. We hypothesized that GK rats would display more severe cerebral damage due to hyperglycemia-aggravated brain injury and, accordingly, more severe cognitive impairments.

To press or not to press? Differential receptor expression and response to novelty in rats learning an operant response for reward.

Learning to perform instrumental tasks is an ability of all animals. In a population of rats, not all individuals will acquire an operant response for reward. We hypothesized that there could be a genetic explanation for differences between High Consumers (those that acquired the lever press response) and Low Consumers (lever press response is low).

The nociceptin/orphanin FQ receptor agonist Ro 64-6198 reduces alcohol self-administration and prevents relapse-like alcohol drinking.

Effects of the opioid receptor like-1 (ORL-1) receptor agonist Ro 64-6198 (0.1, 0.3, and 1.

Identification of neurotransmitter receptor genes involved in alcohol self-administration in the rat prefrontal cortex, hippocampus and amygdala.

About half of the risk to develop alcoholism is related to genetic background and it is well known that alcohol consumption is highly individualized. In this study, we investigated how individual alcohol consumption behaviour in Wistar rats correlated with mRNA expression of 20 genes in the prefrontal cortex, hippocampus and amygdala. We found that the long-term alcohol consumption of an individual could be estimated by the mean of its consumption on Day 2 and 3.

Repeated maternal separation of male Wistar rats alters glutamate receptor expression in the hippocampus but not the prefrontal cortex.

Stress early in life puts the individual at a greater risk for developing mental disorders in adulthood. The animal model of maternal separation involves daily removal of pups from their mother over the early postnatal period and leads to several behavioral deficits in adults. Since this period corresponds to a time of extensive developmental changes in the glutamatergic system, glutamate receptor mRNA expression was studied in the hippocampus and prefrontal cortex.

Impaired long-term habituation is dissociated from increased locomotor activity after sensorimotor cortex compression.

Behavioural habituation to a novel environment is a simple form of learning in rodents. We studied the habituation and locomotor activity (LMA) of Wistar rats subjected to unilateral, transient (30min) extradural compression (EC) of the right sensorimotor cortex. One group of rats was tested every 24h during the first 5 days (D1-D5) post-EC.

Extradural compression of the sensorimotor cortex delays the acquisition but not the recalling of a lever-pressing task in Wistar rats.

The learning and recalling of a lever-press task (LPT) after brief unilateral extradural compression (EC) of the right sensorimotor cortex was studied in Wistar rats. All rats, regardless of the time-point for EC, were trained to lever press for food from D(day)1 to D6. On D8, the position of the active lever was changed to the right side of the operant box and performance was tested until D14.

Behavioural sensitization to nicotine precedes the onset of nicotine-conditioned locomotor stimulation.

Context-dependent behavioural sensitization to nicotine develops faster and is more robust than context-independent sensitization. However, some findings suggest that behavioural sensitization develops irrespective of context. In this study an attempt was made to dissociate the development of context-dependent nicotine sensitization from the onset of nicotine-conditioned locomotor stimulation.

Fluoro-Jade and TUNEL staining as useful tools to identify ischemic brain damage following moderate extradural compression of sensorimotor cortex.

Cerebral ischemia was produced by moderate compression for 30 min of a specific brain area in the sensorimotor cortex of Sprague-Dawley rats. On day 1, that is 24 h after the transient sensorimotor compression, ischemia-exposed animals displayed a marked focal neurological deficit documented as impaired beam walking performance. This functional disturbance was mainly due to contralateral fore- and hind-limb paresis.

The NR2B-selective N-methyl-D-aspartate receptor antagonist Ro 25-6981 [(+/-)-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propanol] potentiates the effect of nicotine on locomotor activity and dopamine release in the nucleus accumbens.

It has been proposed that nicotine-stimulated locomotor activity (LMA) and nicotine-induced dopamine (DA) release in the mesocorticolimbic DA system is partly regulated by glutamate receptors, particularly N-methyl-D-aspartate (NMDA) receptors. The functional characteristics of NMDA receptors depend on their subunit composition (NR1 in combination with NR2A-D). In the present study, we investigated the effect of the NR2B-selective NMDA receptor antagonist Ro 25-6981 [(+/-)-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propanol] on nicotine-stimulated LMA and nicotine-induced DA release in the nucleus accumbens (NAcc) in rats.

Nicotine-induced dopamine release in the nucleus accumbens is inhibited by the novel AMPA antagonist ZK200775 and the NMDA antagonist CGP39551.

Rationale: Accumulated data suggest that N-methyl-D-aspartate (NMDA) receptors are involved in the reinforcing properties of nicotine. However, less is known about the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) receptors in this context.

Objectives: To study the effect of the novel systemically administered AMPA receptor antagonist ZK200775 ([1,2,3,4-tetrahydro-7-morpholinyl-2,3-dioxo-6-(fluoromethyl) quinoxalin-1-yl] methylphosphonate) on nicotine-induced dopamine (DA) release in the nucleus accumbens (NAcc) and nicotine-stimulated locomotor activity (LMA) and particularly the relative role of NMDA and AMPA receptors in nicotine-stimulated DA release and LMA.

The NMDA NR2B subunit-selective receptor antagonist, CP-101,606, enhances the functional recovery the NMDA NR2B subunit-selective receptor and reduces brain damage after cortical compression-induced brain ischemia.

Using a novel in vivo model for cerebral ischemia produced by short-lasting compression of a well-defined brain area of sensorimotor cortex we studied neuroprotective effects of the NMDA NR2B subunit selective antagonist, CP-101,606, in Sprague-Dawley rats. Cortical compression for 30 min produced a consistent and highly reproducible functional impairment, that is paresis of contralateral hind and fore limbs. The neurological deficit was accompanied by marked brain damage in cerebral cortex, hippocampus and thalamus as identified by Fluoro-Jade, a marker of general neuronal cell death.

Loss of GABAergic neuronal phenotype in primary cerebellar cultures following blockade of glutamate reuptake.

Prolonged inhibition of glutamate reuptake by L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a specific glutamate transporter blocker, reduced the number of GABA positive neurons in a primary cerebellar culture by 54%. The disappearance of immunostaining for GABA was gradual and was partially prevented by the N-methyl-D-aspartate (NMDA) receptor blocker, MK-801, and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, NBQX. Combined blockade of NMDA and AMPA receptors restored the original proportion of GABAergic neurons observed in control cultures.

Ethanol differentially inhibits homoquinolinic acid- and NMDA-induced neurotoxicity in primary cultures of cerebellar granule cells.

The potency of ethanol to inhibit N-methyl-D-aspartate (NMDA) receptor functions may depend on the subunit composition of the NMDA receptors. We used a NR2A-B subunit-selective NMDA receptor agonist, homoquinolinic acid (HQ), and a subunit-unselective agonist, NMDA, to induce neurotoxicity in cerebellar granule cells and examined the neuroprotective actions of ethanol, as well as NR2A- and NR2B-subunit selective antagonists, respectively. HQ was a more potent neurotoxic agent than NMDA, as measured by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay.

Cue-induced behavioural activation: a novel model of alcohol craving?

Rationale: Alcohol-associated cues elicit craving in human addicts but little is known about craving mechanisms. Current animal models focus on relapse and this may confound the effect of environmental cues. OBJECTIVES.

Spermidine attenuates the inhibitory effect of ethanol on NMDA-induced neurotoxicity.

The exact site(s) and the molecular mechanism(s) by which ethanol inhibits the activity of NMDA receptors in the brain have so far not been identified although the involvement of several NMDA receptor modulatory sites activated by glycine, Mg2+, Zn2+, polyamines and red-ox agents has been suggested. In this study we investigated the effects of spermidine, a polyamine site agonist, on NMDA-induced neurotoxicity and its ability to modulate the inhibitory action of ethanol on neurotoxicity produced by the maximal neurotoxic concentration of NMDA as measured by the MTT assay in rat cerebellar granule cells. This assay measures the enzymatic activity in mitochondria and/or endosome/lysosome compartment that closely correlates with the cell viability.