Low Exploratory Activity Research Articles

Поведенческие аномалии в генетической модели миодистрофии Дюшенна у мышей

Mutations in the Dmd gene encoding the membrane protein dystrophin are associated with the development of severe X-linked muscle diseases Duchenne and Becker myodystrophy. At the same time, along with the classic symptoms of striated muscles, dystrophin mutations can lead to a decrease in cognitive functions and behavioral abnormalities. Objective: conducting a pilot analysis of behavioral and cognitive characteristics in mice with a genetic defect that reproduces the phenotype of Duchenne myodystrophy. Materials and methods. To assess the features of motor functions and behavior, DmdDel8-34(n=13) and control animals of the wild type (n=12) were subjected to research in the tests "Load retention", "Rotarod", "Elevated plus maze" and "Object recognition". Results. It was found that mice carrying the DmdDel8-34 mutation are characterized by a decrease in motor functions, show signs of anxiety, and also show low exploratory activity. The detected features of the cognitive and emotional status are consistent with clinical observations indicating an increased risk of developing autism spectrum disorders and obsessive-compulsive disorder in patients with Dmd gene mutations. Thus, it was proved that from the 8th week of life, mice of the DmdDel8-34 line show a decrease in performance in the Rotarod and Load Retention tests. Behavioral testing in the Elevated Plus Maze test revealed a decrease in time reaching a statistically significant difference compared to the wild-type control at week 12, and when assessing cognitive functions in the Object Recognition test, it was shown that DmdDel8-34mice show an increase in the discrimination index value, which is a sign of increased efficiency of hippocampal memory. Conclusion. The study made it possible to identify some behavioral anomalies in genetically modified mice carrying a large deletion of exons 8-34 of the Dmd gene encoding dystrophin.

P.0238 Effect of neuropeptide s on ultrasonic vocalizations in rats: individual differences by trait-wise low vs. high exploratory activity

P.0238 Effect of neuropeptide s on ultrasonic vocalizations in rats: individual differences by trait-wise low vs. high exploratory activity

Effect of Neuropeptide S Administration on Ultrasonic Vocalizations and Behaviour in Rats with Low vs. High Exploratory Activity.

Neuropeptide S (NPS) is a peptide neurotransmitter that in animal studies promotes wakefulness and arousal with simultaneous anxiety reduction, in some inconsistency with results in humans. We examined the effect of NPS on rat ultrasonic vocalizations (USV) as an index of affective state and on behaviour in novel environments in rats with persistent inter-individual differences in exploratory activity. Adult male Wistar rats were categorised as of high (HE) or low (LE) exploratory activity and NPS was administered intracerebroventricularly (i.c.v.) at a dose of 1.0 nmol/5 µL, after which USVs were recorded in the home-cage and a novel standard housing cage, and behaviour evaluated in exploration/anxiety tests. NPS induced a massive production of long and short 22 kHz USVs in the home cage that continued later in the novel environment; no effect on 50 kHz USVs were found. In LE-rats, the long 22 kHz calls were emitted at lower frequencies and were louder. The effects of NPS on behaviour appeared novelty- and test-dependent. NPS had an anxiolytic-like effect in LE-rats only in the elevated zero-maze, whereas in HE-rats, locomotor activity in the zero-maze and in a novel standard cage was increased. Thus NPS appears as a psychostimulant peptide but with a complex effect on dimensions of affect.

Interference Competition for Mutualism between Ant Species Mediates Ant-Mealybug Associations.

Ant-hemipteran mutualism has been well documented, and many studies have reported the interference competition between ant species for the mutualism. However, little is known on how this interference competition impacts the reciprocally beneficial association. Previous studies demonstrated that the invasive mealybug Phenacoccus solenopsis (Tinsley) has established close mutual relationship with the ghost ant Tapinoma melanocephalum (Fabricius). The sympatric ants, Paratrechina longicornis (Latreille) and Tetramorium bicarinatum (Nylander) were frequently observed to compete for nutrient honeydew produced by P. solenopsis with T. melanocephalum. Herein, we investigated the effects of interference competition between the ant species on the ant-mealybug interactions. Phenacoccus solenopsis benefited from the tending by T. melanocephalum and P. longicornis. Interference competition between T. melanocephalum and P. longicornis interrupted the mutualism, suppressed the trailing activity of both species, but negligibly influenced the parasitism of Aenasius bambawalei Hayat, a solitary endoparasitoid of P. solenopsis. Harmonia axyridis, a predator of P. solenopsis, showed a significant avoidance when encountering with T. melanocephalum or P. longicornis, but not T. bicarinatum. Ant workers showed higher aggressiveness and lower exploratory activity when T. melanocephalum encountered P. longicornis. However, competition between T. melanocephalum and T. bicarinatum seldom influenced the trailing and exploratory activity of T. melanocephalum. It is concluded that interference competition for mutualism between ant species can mediate ant-mealybug associations and the fitness of mealybug colony. Our results also demonstrate that the effects of interference competition between ant species on ant-mealybug mutualism are varied among ant species.

A selective peroxisome proliferator-activated receptor-γ agonist benefited propionic acid induced autism-like behavioral phenotypes in rats by attenuation of neuroinflammation and oxidative stress

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in children. It is diagnosed by two main behavioral phenotypes i.e. social-communication impairments and repetitive behavior. ASD is complex disorder with unsolved etiology due to multiple genes involvement, epigenetic mechanism and environmental factors. The clinical and preclinical studies have been indicating the association of propionic acid with autism spectrum disorder. Numerous studies suggest the potential therapeutic effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in different brain disorders. This research evaluates the utility of selective agonist of PPAR-γ, pioglitazone in postnatal propionic acid induced ASD related symptomatology in male Wistar rats. PPA (250 mg/kg, p.o.) was administered to male offspring for three consecutive days from postnatal 21st day to 23rd day. PPA induced social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity in rats. Also, postnatal propionic acid-treated rats showed higher levels of oxidative stress (increased in thiobarbituric acid reactive species and decreased in reduced glutathione) as well as inflammation (increased in interleukin-6, tumor necrosis factor-alpha and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. The rats were treated daily with pioglitazone (10 mg/kg and 20 mg/kg, p.o.) from postnatal 24th day to end of the study. Treatment with pioglitazone, significantly attenuated the postnatal propionic acid-induced social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, pioglitazone also reduced the postnatal propionic acid-induced oxidative stress and neuroinflammation in aforementioned brain regions. Hence, pioglitazone improved the propionic acid-induced neurobehavioral and biochemical impairments in rats.

Beneficial effects of pioglitazone, a selective peroxisome proliferator-activated receptor-γ agonist in prenatal valproic acid-induced behavioral and biochemical autistic like features in Wistar rats

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in children. It is diagnosis by two main behavioral phenotypes i.e. social-communication impairments and repetitive behavior. ASD is complex disorder with unsolved etiology due to multiple genes involvement, epigenetic mechanism and environmental factors. Valproic acid (VPA), a teratogen is known to induce characteristic features related to ASD in rodents. Numerous studies suggest the potential therapeutic effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in different brain disorders. This research evaluates the utility of selective agonist of PPAR-γ, pioglitazone in prenatal VPA induced experimental ASD symptomatology in Wistar rats. The prenatal administration of VPA has induced social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity in rats. Also, prenatal VPA-treated rats have shown higher levels of oxidative stress (increased in thiobarbituric acid reactive species, and decreased in reduced glutathione level) and inflammation (increased in interleukin-6, tumor necrosis factor-alpha and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. Treatment with pioglitazone significantly attenuated the prenatal VPA-induced social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, pioglitazone also reduced the prenatal VPA-induced oxidative stress and neuroinflammation in aforementioned brain regions. Hence, it may be concluded that pioglitazone may provide neurobehavioral and biochemical benefits in prenatal VPA-induced autistic phenotypes in rats.

Benefits of Fenofibrate in prenatal valproic acid-induced autism spectrum disorder related phenotype in rats

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with two major behavioral symptoms i.e. repetitive behavior and social-communication impairment. The unknown etiology of ASD is responsible for the difficulty in identifying the possible therapeutic modulators for ASD. Valproic acid (VPA) is an anticonvulsant drug in both human and rodents with teratogenic effects during pregnancy. Therefore, prenatal exposure of VPA induced autism spectrum disorder like phenotypes in both human and rodents. Peroxisome proliferator-activated receptor-alpha (PPAR-α) is widely localized in the brain. This research investigates the utility of fenofibrate, a selective agonist of PPAR-α in prenatal VPA-induced experimental ASD in Wistar rats. The prenatal VPA has induced social impairment (three chambers social behavior apparatus), repetitive behavior (Y-maze), hyperlocomotion (actophotometer), anxiety (elevated plus maze) and low exploratory activity (hole board test). Also, prenatal VPA treated rats have shown higher levels of oxidative stress (increased in thiobarbituric acid reactive species and decreased in reduced glutathione level) and inflammation (increased in interleukin-6, tumor necrosis factor-α and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. Treatment with fenofibrate significantly attenuated prenatal VPA-induced social impairment, repetitive behavior, hyperactivity, anxiety, and low exploratory activity. Furthermore, fenofibrate also decreased the prenatal VPA-induced oxidative stress and inflammation in brain regions. Hence, it may be concluded that fenofibrate may provide neurobehavioral and biochemical benefits in prenatal VPA-induced autism phenotypes in rats.

Selective modulator of peroxisome proliferator-activated receptor-α protects propionic acid induced autism-like phenotypes in rats

AimsThe present study investigated the neuropharmacological role of PPAR-α modulator, fenofibrate in postnatal-propionic acid induced symptomatology related with autism spectrum disorders (ASD) in Wistar rats. Main methodsThe propionic acid (250 mg/kg, p.o.) was administered to rats from postnatal 21st day to 23rd day to induce autism-related neurobehavioral and neurobiochemical alterations in rats. Then, rats were treated with fenofibrate (100 mg/kg and 200 mg/kg, orally) from postnatal 24th day till 48th day. The social behavior (three chambers social testing apparatus), repetitive behavior (Y-maze), locomotor activity (actophotometer), anxiety (elevated plus maze) and exploratory behavior (hole board test) were assessed. Biochemically, oxidative stress (thiobarbituric acid reactive species and reduced glutathione level) and neuroinflammation (interleukin-6, tumor necrosis factor-α and interleukin-10) were evaluated in the cerebellum, brainstem and prefrontal cortex of rats. Key findingsPropionic acid-treated rats showed social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity. Also, these animals showed higher levels of oxidative stress (increased in thiobarbituric acid reactive species and decreased in reduced glutathione level) as well as inflammation (increased in interleukin-6, tumor necrosis factor-α and decreased in interleukin-10) and inflammation in aforementioned brain-regions. Treatment with fenofibrate significantly attenuated the propionic acid induced-social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, fenofibrate also reduced the oxidative stress and neuroinflammation in propionic acid-treated rats. SignificanceA selective PPAR-α agonist, fenofibrate provides neurobehavioral and neurobiochemical benefits in postnatal-propionic acid induced autism-related phenotype in rats. Thus, fenofibrate may further be studied for its possible benefits in ASD symptoms.

Method for Studies of Orientation and Exploratory Behavior in Humans. Effects of Emotional Stress.

We developed a new experimental model for studies of orientation and exploratory behavior in humans. This method allows analysis of variants of orientation and exploratory behavior in humans, including risky behavior, and cognitive and individual typological parameters. The model allows distinguishing examinees with high and low orientation and exploratory activity, which helps to determine their psychoemotional status. Surprisingly, individuals in emotional strain demonstrated longer orientation and exploratory behavior. This allows them to achieve the results more rapidly during purposeful behavior under similar conditions. This model provides the tool for evaluation of the electrophysiological, autonomic, and biochemical mechanisms of orientation and exploratory behavior of humans.

Transformation of catalytic characteristics of cerebral monoamine oxidases in experimental posttraumatic stress disorders.

We studied the contribution of the transformation of the catalytic properties of cerebral monoamine oxidase in the development of behavioral disorders during stress. Monoamine oxidase activities and catalytic characteristics, LPO intensity, and oxidative modification of proteins in suspension of the brain mitochondria were evaluated over the course of experimental posttraumatic stress disorder. The detected shifts were comparable with the results of neuroethologic testing. The development of behavioral disorders presented by low exploratory activity and high anxiety was associated with transformation of catalytic characteristics of cerebral monoamine oxidases, associated with the development of oxidative stress with predominant intensification of metal-catalyzed protein oxidation.

Differences in extracellular glutamate levels in striatum of rats with high and low exploratory activity.

Major inter-individual differences exist in vulnerability to anxiety and affective disorders, and the underlying neurobiology could help in understanding the predisposition to these disorders and treatment resistance. Recently the glutamatergic system has become a target in the development of novel antidepressants. We compared extracellular glutamate levels in low (LE-) and high exploring (HE-) rats in hippocampus and striatum at baseline and after inhibition of re-uptake by perfusion with l-trans-pyrrolidine-2,4-dicarboxylate (PDC, 4mM). Glutamate levels in microdialysates were measured by HPLC after derivatization. In the striatum, baseline glutamate levels in young adult LE-rats and HE-rats were not significantly different, but the response to uptake inhibition was: perfusion with PDC increased extracellular glutamate levels in both LE- and HE-rats, but to a significantly lower extent in LE-rats. Although the characteristic levels of exploration of LE- and HE-rats had previously been shown to be stable up to 8 months of age, we identified a subgroup of HE-rats whose exploration levels had drastically dropped by age of 11 months (formerly HE-rats, HEF), and analyzed their data separately. There were no differences in the PDC-evoked striatal glutamate release between the three groups; however, the baseline glutamate levels were higher in the HEF-subgroup compared to the HE- and LE-animals. In the CA1 area of hippocampus, there were no differences in extracellular glutamate levels between the LE- and HE-rats either at baseline or after inhibition of uptake. These results suggest that inter-individual differences in exploratory behaviour may be related to striatal glutamatergic neurotransmission.

Differences in 5-HT1A receptor-mediated hypothermia in rats with low or high exploratory activity

Alterations in the serotonin (5-HT) system and the 5-HT1A receptor function have a significant role in anxiety-related and depression-related states. This study investigated the stress-induced hyperthermia (SIH) response and sensitivity to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetraline in rats with persistently low or high levels of exploratory activity (LE and HE, respectively), of which the LE rats show more anxiety-like and depressive-like phenotypes. No differences in the SIH in response to novel cage or injection stress were found using rectal temperature measurements. However, the LE rats had significantly less pronounced decreases in SIH in response to the 0.3 mg/kg dose of 8-hydroxy-2-(di-n-propylamino)-tetraline. Exploratory behaviour correlated significantly and positively with the magnitude of change in body temperature in response to the 5-HT1A receptor agonist. This finding suggests a less effective 5-HT1A function in the LE rats and implicates the 5-HT1A receptor in the anxiety component of passive behaviour in novel surroundings.

Relation of exploratory behaviour to plasma corticosterone and Wfs1 gene expression in Wistar rats

Male Wistar rats exhibit significant variations in exploratory behaviour in the elevated plus-maze (EPM) model of anxiety. We have now investigated the relation between exploratory behaviour and levels of corticosterone and systemic oxidative stress. Also, the expression levels of endocannabinoid-related and wolframin (Wfs1) genes were measured in the forebrain structures. The rats were divided into high, intermediate and low exploratory activity groups. Exposure to EPM significantly elevated the serum levels of corticosterone in all rats, but especially in the high exploratory group. Oxidative stress indices and expression of endocannabinoid-related genes were not significantly affected by exposure to EPM. Wfs1 mRNA level was highly dependent on exploratory behaviour of animals. In low exploratory activity rats, Wfs1 gene expression was reduced in the temporal lobe, whereas in high exploratory activity group it was reduced in the mesolimbic area and hippocampus. Altogether, present study indicates that in high exploratory activity rats, the activation of brain areas related to novelty seeking is apparent, whereas in low exploratory activity group the brain structures linked to anxiety are activated.

Regulation of extracellular serotonin levels and brain-derived neurotrophic factor in rats with high and low exploratory activity

Serotonin (5-HT) system has a significant role in anxiety- and depression-related states and may be influenced by brain-derived neurotrophic factor (BDNF). This study examined extracellular 5-HT levels and expression of BDNF in rats with persistently low or high levels of exploratory activity (LE and HE, respectively). Baseline extracellular levels of 5-HT as assessed by in vivo microdialysis in conscious animals were similar in both groups in medial prefrontal cortex (PFC) and dentate gyrus (DG). No differences were found in parachloroamphetamine-induced 5-HT release in either region. However, LE animals had significantly higher levels of 5-HT transporter (5-HTT) binding in PFC and a larger increase in extracellular 5-HT levels after administration of citalopram (1 μM) into this area by retrograde dialysis. No difference in 5-HTT levels was found in hippocampus, while perfusion with citalopram was accompanied by a greater increase in extracellular 5-HT in the HE group in this brain region. LE-rats had higher levels of BDNF mRNA in the PFC but not hippocampus. In contrast, levels of nerve growth factor mRNA were similar in these brain regions of LE- and HE-rats. The differential regulation of 5-HT-ergic system in LE- and HE-rats in PFC and hippocampus may form the basis for their distinct anxiety-related behaviours.

Screen for genes in periaqueductal grey of male Wistar rats related to reduced exploratory activity in the elevated plus-maze

Aim of a present study was to find genes in the periaqueductal grey (PAG) related to the exploratory behavior in rats. Male Wistar rats were divided according to their exploratory behavior in the elevated plus-maze model of anxiety into two groups: high (non-anxious) and low (anxious) exploratory activity. Differential expression of genes was analyzed using the cDNA representational difference analysis (RDA). Q-RT-PCR was used to confirm most prominent changes and functional annotation of the identified genes was performed to establish pathways related to exploratory behavior of rats. We found different genetic activation related to the exploratory activity of rats. Rats with low exploratory activity showed increase in the intracellular signal transduction and in GABA, vasopressin and adrenergic receptor activities. Functional annotation confirmed significant induction of cAMP system and GTPases in rats with anxious-type behavior. On the other hand, rats with high exploratory activity in the elevated plus-maze (non-anxious type of behavior) had increased activity of genes forming “behavioral fear response” system. These changes were specific to PAG, because they were not found in the cerebellum. In addition, plasma corticosterone levels were significantly higher in rats with non-anxious behavior compared to anxious behavior. Our results show that non-anxious behavior is related to activation of “fear response system” and more intense activation of HPA axis. Possibly it means that this system helps animals to cope with the threatening circumstances. More detailed analysis of this potential “fear response system” is necessary in the further studies for understanding its role in the regulation of emotional behavior.

Cerebral oxidative metabolism in rats with high and low exploratory activity

To reveal brain regions most significantly related to individual differences in exploratory behaviour, oxidative metabolism was measured by cytochrome c oxidase histochemistry in 2 months old Wistar rats with persistently high (HE) or low (LE) exploratory activity in a novel environment. LE-rats had significantly higher levels of oxidative metabolism in dorsal raphe and inferior colliculi. In contrast, HE-rats had higher metabolic activity in entorhinal cortex. In conclusion, rats with different exploratory styles differ in underlying cerebral activity as measured via oxidative metabolism in regions implicated in defensive behaviours and cognitive processing of sensory stimuli.

Rats displaying distinct exploratory activity also have different expression patterns of γ-aminobutyric acid- and cholecystokinin-related genes in brain regions

The aim of the present study was to evaluate the expression of genes in relation to the exploratory activity of rats. Limbic system-associated membrane protein (LsAMP) gene, γ-aminobutyric acid-(GABA)- and cholecystokinin-(CCK)-related genes were analyzed in the frontal cortex, amygdala and periaqueductal gray (PAG) after exposure of rats to exploratory challenge. Two groups of animals displaying low and high exploratory activity in the elevated plus-maze were selected for gene expression studies from the population of 43 male Wistar rats. Eight rats were taken randomly from the same cages as animals exposed to the plus-maze, but they were not subjected to the exploratory test. This home-cage control group was also used for gene expression analysis in order to explore a possible impact of the plus-maze exposure. Rats with low and high exploratory activity displayed clearly distinct profiles in gene expression. Most prominent alterations were established in the amygdala where almost all GABA-related and CCK receptor genes were two- to five-fold up-regulated in low exploratory activity rats compared to high exploratory activity and home-cage control group. The expression of several GABA-related genes was also increased in the PAG of animals displaying low exploratory activity compared to the other groups. Moreover, we found reduced expression of GABA- and CCK-related genes in all three brain regions in animals with high exploratory activity compared to the home-cage control group. In addition to these findings, we established a significantly increased expression of the LsAMP gene in the amygdala and PAG of low exploratory activity animals compared with the other groups. In conclusion, low and high exploratory activity rats differed not only by their exploratory activity but also displayed opposite gene expression patterns. Low exploratory activity of rats correlated with the up-regulation of LsAMP and GABA-related genes in the amygdala and PAG and with the up-regulation of CCK receptors in the amygdala. High exploratory activity of rats was related to a significant down-regulation of CCK receptor genes in the amygdala and PAG. These rats also displayed the reduced expression of GABA-related genes in the frontal cortex and PAG.

Spatial memory deficits in middle‐aged mice correlate with lower exploratory activity and a subordinate status: role of hippocampal neurotrophins

The aim of the present work was to relate age-related individual differences in cognitive function with behavioural strategies employed in social and non-social challenges. To this purpose, the behaviour of adult (5-month-old) and middle-aged (13-month-old) CD-1 mice was scored in the social interaction, plus-maze, Morris water maze (MWM) and open-field tests. In addition, brain levels of nerve growth factor and brain-derived neurotrophic factor (BDNF) were analysed and correlated with the behaviours scored. Compared to adults, middle-aged mice showed greater anxiety in both non-social and social situations, spending less time in the open arms of the plus-maze and performing more freezing behaviour in response to aggression. Based upon their behaviour in the social interaction test, adult and middle-aged subjects were classified as dominant or subordinate and their behaviour in the open field, plus-maze and MWM tests subjected to factor analysis, taking into account age and social status. Results highlighted meaningful differences in exploratory strategies as a function of social status only in middle-aged subjects. In particular, middle-aged dominants were, overall, more explorative than same-aged subordinates, spending less time in peripheral areas and approaching more readily a novel object. Interestingly, in middle-aged mice, superior performance in the MWM task was associated with exploratory strategies exploited by dominants. At adulthood, BDNF hippocampal levels, but not specific behaviours, were positively correlated with the ability to learn a spatial task. Overall, data indicate that, in middle-aged subjects individual differences in exploratory strategies, rather than neurotrophin levels, are able to predict the degree of impairment in a spatial learning task.

Effects of low dose N-(2-chloroethyl)- N-ethyl-2-bromobenzylamine administration on exploratory and amphetamine-induced behavior and dopamine D 2 receptor function in rats with high or low exploratory activity

Individual differences in behavioral traits are associated with sensitivity to various neurochemical and psychopharmacological manipulations. In this study exploratory and amphetamine-induced behavior in rats with persistently high or low exploratory activity (HE and LE, respectively) was examined before and after a partial denervation of the locus coeruleus (LC) projections with the selective neurotoxin DSP-4 ( N-(2-chloroethyl)- N-ethyl-2-bromobenzylamine; 10 mg/kg). Partial LC denervation prevented the increase in exploratory activity over repeated test sessions in the LE animals, but had no effect in HE-rats. Amphetamine- (0.5 mg/kg) induced locomotor activity was attenuated by DSP-4 pretreatment only in HE-rats. These results suggest differential involvement of LC noradrenergic transmission in novelty- and amphetamine-induced behavior in animals with persistent differences in novelty-related behavior. In addition to partial noradrenaline depletion in the frontal cortex and hippocampus, which occurred in both HE- and LE-rats, DSP-4 treatment also decreased the content of dopamine and its metabolites in the nucleus accumbens, and the metabolite levels in striatum, but only in the LE-animals. 5-HIAA levels were also reduced in the nucleus accumbens and striatum in LE-rats by the neurotoxin. D 2 receptor function, as determined by dopamine-stimulated [ 35S]GTPγS binding, was increased by DSP-4 treatment in the striatum of LE-rats, but reduced in HE-rats. No effect of partial LC denervation was found on dopamine-stimulated [ 35S]GTPγS binding in the nucleus accumbens. Together these findings suggest that LC noradrenergic neurotransmission is differently involved in dopaminergic mechanisms which mediate novelty-related vs amphetamine-induced behavior.

P.6.013 Effect of partial locus coeruleus denervation on behavioural sensitization to amphetamine and dopamine D2 receptor-G protein interaction in rats with high or low exploratory activity

P.6.013 Effect of partial locus coeruleus denervation on behavioural sensitization to amphetamine and dopamine D2 receptor-G protein interaction in rats with high or low exploratory activity