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Biomedical subjects

M Le Moal

Publications and source records attributed to M Le Moal.

At least 109 records · Page 6Linked to original sources
PubMed1996

Changes in striatal immediate early gene expression following neonatal dopaminergic lesion and effects of intrastriatal dopaminergic transplants.

To evaluate the functional integration of neonatal dopaminergic transplants within host brain we studied the postsynaptic effects induced by their stimulation by following the expression of immediate early genes c-fos, c-jun and egr-1. This study was conducted nine months after the intrastriatal implantation of embryonic mesencephalic neurons to rat pups having sustained a unilateral lesion of the nigrostriatal dopaminergic system. We examined whether, when challenged with d-amphetamine: (1) dopaminergic grafts transplanted into the previously denervated neonatal neostriatum lead to a normal activation of postsynaptic striatal neurons in term of immediate early genes activation; and (2) whether this activation is related to the action of the dopamine released from the grafts using a dopaminergic D1 antagonist. Following a mild stress-injection of saline-c-fos expression was high in the lesioned neostriatum when compared with control animals. This effect was only partially counteracted by a pre-treatment with the D1 antagonist SCH 23390, but was abolished by the graft. Administration of d-amphetamine increased c-fos expression in the neostriatum and the globus pallidus of the control group. This activation was partially blocked by the lesion. The transplant reversed the effect of the lesion and, moreover, led to a c-fos over-expression in the dorsolateral neostriatum and the globus pallidus. These overcompensations positively correlated with the abnormal rotation induced by d-amphetamine in the same animals. Pre-treatment with SCH 23390 blocked the effect of d-amphetamine on c-fos expression in control and grafted animals. Similar results were found for egr-1 but not c-jun expression. It is concluded that the neonatal lesion of the nigrostriatal dopaminergic pathway, in contrast to the adult-stage lesion, modifies the reactivity of c-fos in the neostriatum to stress, presumably in relation with compensatory reorganizations occurring following the neonatal lesion. Grafts made into neonates, when challenged with amphetamine, induce an abnormal c-fos expression which can predict the degree of overshoot observed for rotation activity. This over-expression, which depends upon the stimulation of D1 receptors, indicate an abnormal activation of postsynaptic target cells by the grafts.

Amino Acid Sequence↗
PubMed1996

Hippocampal type I and type II corticosteroid receptors are differentially regulated by chronic prazosin treatment.

Two types of hippocampal corticosteroid receptors play an important role in regulating the secretion of corticosterone: type I receptors are thought to regulate both the basal and stress induced release of corticosterone whereas type II receptors seem to be involved only in the stress response. Although these receptors are known to be regulated by circulating levels of corticosterone, there is also evidence for a direct neural control independent of hormonal influences. Furthermore, several studies suggest differential regulation of type I and type II corticosteroid receptors, with greater hormonal control of type II and greater neural control of type I. In order to investigate this theory of differential regulation of type I and type II corticosteroid receptors, we studied the effect of chronic treatment with either vehicle or the alpha 1 noradrenergic antagonist prazosin (0.5 mg/kg, i.p), on hippocampal corticosteroid receptors. Rats in one group had intact adrenal glands, whereas rats in a second group were adrenalectomized, their plasma corticosterone levels being maintained in the physiological range by implantation of corticosterone pellets. Thus, in the first group, the effects of drug-induced changes in both noradrenergic transmission and corticosterone secretion on corticosteroid receptors were investigated, whereas in the second group, the influence of altered noradrenergic transmission was effectively isolated. The results of this experiment show that, in comparison to the vehicle treatment, chronic treatment with the alpha 1 receptor antagonist prazosin decreased the number of type I corticosteroid receptors in adrenalectomized animals with corticosterone substitutive therapy. This effect on type I was not evident in adrenal-intact animals. In contrast, the prazosin treatment reduced the number of type II corticosteroid receptors in adrenal-intact animals, but not in adrenalectomized animals with corticosterone substitutive therapy. It has also been demonstrated here that, in the adrenal-intact animals, chronic prazosin induces hypersecretion of corticosterone after stress, which may account for the reduction of type II corticosteroid receptors noted in this group. Taken together, these results support the theory that type I and type II are differentially regulated: type I receptors can be regulated by noradrenaline independently of corticosterone, whereas type II receptors seem to be adjusted by circulating levels of corticosterone. These results may also suggest possible pharmacotherapies of hypothalamo-pituitary-adrenal axis dysregulation, such as that occurring during depression, Alzheimer's disease and Cushing syndrome, by targeting type I corticosteroid receptors.

Adrenalectomy↗
PubMed1996

Behavioral reactivity to novelty during youth as a predictive factor of stress-induced corticosterone secretion in the elderly--a life-span study in rats.

Inter- and intra-individual differences in hypothalamo-pituitary adrenal (HPA) axis activity and behavioral reactivity to novelty between young and old rats were evidenced in this longitudinal life-span study. Higher responders to novelty (HR) had a higher corticosterone secretion which showed a quicker increase with age than did the others (LR); the differences in response to novelty observed in youth were no longer apparent in the old rats. Response to novelty in youth is a predictive factor of accelerated aging of the HPA axis. These early changes, which precede the appearance of the memory deficits, may be a causal factor. Disappearance of behavioral and endocrinological inter-individual differences at 21 months highlights the importance of not restricting aging studies to old subjects.

Aging↗
PubMed1996

Serotonin enhances striatal dopamine outflow in vivo through dopamine uptake sites.

Serotonin (5-HT) administered at 1, 3, and 10 microM into the striatum of halothane-anesthetized rats by in vivo microdialysis increased extracellular dopamine (DA) in a concentration-dependent manner (approximately 65, 190, and 440%, respectively). These effects were reduced by 50% in the presence of 1 microM tetrodotoxin (TTX) or in the absence of Ca2+ ions. The DA uptake blocker nomifensine (0.1 microM) significantly lowered (by 50%) the enhancement of DA outflow induced by 3 microM 5-HT. Nomifensine (1 microM) coperfused with 1 microM TTX abolished the 1 and 3 microM 5-HT-induced DA outflow, whereas the effect of 10 microM 5-HT was significantly reduced by 1 (-55%) and 10 micro M (-70%) nomifensine. These data demonstrate that, in vivo, striatal DA uptake sites are partially involved in the DA-releasing action of 5-HT.

Animals↗
PubMed1996

Phenotype of striatal cells expressing c-Fos following amphetamine treatment of rats with intrastriatal dopaminergic grafts.

Activation of the nigrostriatal dopaminergic system by psychostimulants such as amphetamine increases c-Fos expression in the striatum, mostly in the striatonigral substance P-ergic pathway. This effect is greatly reduced in the neostriatum deprived of dopaminergic afferents. Dopaminergic grafts implanted into the denervated neostriatum restore the reactivity of the striatum to amphetamine. However, the number of striatal neurons expressing c-Fos is greatly increased in the graft-bearing striatum compared with the normal striatum. We examined whether this increase in the number of c-Fos-expressing neurons corresponds to the recruitment of a new neuron population, or whether it reflects an increase in the proportion of substance P-ergic neurons exhibiting activation of c-Fos. Adult rats received a unilateral 6-hydroxydopamine lesion of the ascending dopaminergic mesotelencephalic pathway, and a suspension of embryonic mesencephalic neurons was subsequently implanted into the denervated neostriatum. Three months after implantation, animals were injected with d-amphetamine (5 mg/kg) and killed 2 h later. In the first experiment, striatal sections were processed to visualize both c-Fos protein, by immunohistochemistry, and preproenkephalin A or substance P, by in situ hybridization. In the second experiment, c-Fos and neuropeptide Y were visualized on the same sections. In addition, some sections incubated with anti-c-Fos antibody were counterstained with toluidine blue in order to determine whether cholinergic neurons were expressing c-Fos following amphetamine treatment. The density of neurons expressing c-Fos following amphetamine treatment was three-fold higher in the graft-bearing striata than in the striata of control animals. Approximately 75% of the c-Fos expressing cells were substance P-ergic in control animals whereas 6% were enkephalinergic and only a few were neuropeptide Y-ergic or cholinergic. Similar proportions were found in the graft-bearing striatum, signifying that the pattern of activation of c-fos following amphetamine administration is not changed by the graft. Thus, the increased expression of c-Fos predominantly reflects a graft-induced increase in the proportion of neurons expressing c-Fos within the same population of neurons which normally expresses c-Fos in the striatum, i.e. the striatonigral substance P-ergic neurons; there is no recruitment of a new neuronal population. This increased activation of the striatonigral substance P-ergic pathway may underlie the abnormal behavioural reactions brought about by amphetamine-induced stimulation of the implanted dopaminergic neurons.

Amphetamine↗
PubMed1996

Novelty-seeking in rats--biobehavioral characteristics and possible relationship with the sensation-seeking trait in man.

A behavioral trait in rats which resembles some of the features of high-sensation seekers in man has been characterized. Given that the response to novelty is the basis of the definition of sensation-seeking, individual differences in reactivity to novelty have been studied on behavioral and biological levels. Certain individuals labeled as high responders (HR) as opposed to low responders (LR) have been shown to be highly reactive when exposed to a novel environment. These groups were investigated for free-choice responses to novel environments differing in complexity and aversiveness, and to other kinds of reinforcement, i.e. food and a drug. The HR rats appeared to seek novelty, variety and emotional stimulation. Only HR individuals have been found to be predisposed to drug-taking: they develop amphetamine self-administration whereas LR individuals do not. They also exhibit a higher sensitivity to the reinforcing properties of food. On a biological level, compared to LR rats, HR animals have an enhanced level of dopaminergic activity in the nucleus accumbens both under basal conditions or following a tail-pinch stress. HR and LR rats differ in reactivity of the corticotropic axis: HR rats exposed to a novel environment have a prolonged secretion of corticosterone compared to LR rats. The association of novelty, drug and food seeking in the same individual suggests that these characteristics share common processes. Differences in dopaminergic activity between HR and LR rats are consistent with results implicating these dopaminergic neurons in response to novelty and in drug-taking behavior. Given that rats self-administer corticosterone and that HR rats are more sensitive to the reinforcing properties of corticosteroids, it could be speculated that HR rats seek novelty for the reinforcing action of corticosterone. These characteristics may be analogous to some for the features found in human high-sensation seekers and this animal model may be useful in determinating the biological basis of this human trait.

Animals↗
PubMed1996

Evidence for selective involvement of dopamine D1 receptors of the ventral tegmental area in the behavioral sensitization induced by intra-ventral tegmental area injections of D-amphetamine.

The induction of behavioral sensitization to D-amphetamine (AMPH) is known to result at least in part from an action of the drug in the ventral tegmental area (VTA), which contains the dopamine (DA) A10 cell bodies. To specify the cellular mechanisms through which AMPH acts in the VTA and leads to behavioral sensitization after repeated intra-VTA injections, the involvement of VTA DA D1 and D2 and serotonin2 receptors in this phenomenon was investigated in independent experiments. The results reported here confirm that repeated intra-VTA AMPH injections (four injections of 5 micrograms/0.5 microliter every other day) induce behavioral sensitization, as revealed by the potentiation of the locomotor response to peripheral challenges with AMPH (0.5 mg/kg) 4 or 15 days after treatment. This behavioral sensitization induced by intra-VTA administration of AMPH cross-reacts with morphine (1 microgram/0.5 microliter) administered into the VTA 7 days after treatment. We demonstrated that the D1 receptor antagonist (R)-(+)-8-chloro-2,3,4, 5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (0, 0.01, 0.1 and 1 microgram/ 0.5 microliter) coadministered in the VTA with AMPH dose-dependently prevents the behavioral sensitization to peripheral AMPH challenges (at either 4 or 15 days after treatment) as well as the cross-sensitization with intra-VTA morphine. Neither DA D2 nor serotonin2 receptor blockade, using sulpiride (10 micrograms/0.5 microliters) and ketanserin (1 micrograms/0.5 microliters), respectively, had any effect on the induction of behavioral sensitization. In conclusion, these results demonstrate the selective involvement of VTA DA D1 receptors in the process by which AMPH acts in the VTA to induce behavioral sensitization.

Animals↗
PubMed1995

Control of HPV 18 DNA replication by cellular and viral transcription factors.

Papillomavirus replication in vivo requires the interaction of the virally encoded proteins E1 and E2 with the origin of replication which is localised in the regulatory region (long control region or LCR) of the viral genome. In genital human papillomaviruses (HPVs), the origin overlaps promoter elements of early transcription. In this study, we analysed the replication of HPV18 DNA using the complete LCR containing mutations in transcription regulatory elements. We found that each of the three E2 binding sites proximal to the AT-rich sequence of the origin contributes to the replication rate of DNA, although not identically. In addition, two sequences important for early transcription, an Sp1 binding site and the TATA box, were also found to play a role in replication. In contrast, two AP1 binding sites required for the enhancer-mediated activation of early transcription did not affect the replication, while other upstream sequences in the LCR did contribute to the replication efficiency. Our results indicate that besides a core origin of replication containing an AT-rich sequence and three E2 binding sites, auxiliary elements affect HPV18 DNA replication in the context of the full length LCR, some of which are important for transcription.

Adenovirus E2 Proteins↗
PubMed1995

Social stress increases the acquisition of cocaine self-administration in male and female rats.

The effect of social stress on the vulnerability to commence cocaine self-administration was examined in Sprague-Dawley rats repeatedly exposed to aggressive attack by a same-sex opponent. Both sexes were studied, since the factors influencing the acquisition of drug self-administration in females have not been defined. Male and female rats encountered an aggressive male or lactating female opponent on four separate occasions over the course of one week. Control male and female rats were not exposed to attack. All animals were implanted with jugular catheters, and six days later placed into the self-administration box, where a nose-poke in the designated 'active hole' resulted in a 20 microliters injection of cocaine (0.32 mg/kg). Nose-pokes in an 'inactive' hole had no effect. Male and female rats that had experienced social stress self-administered more cocaine than non-defeated controls. The difference between the stressed and non-stressed animals in the number of cocaine injections was not present during the first few days of exposure to cocaine, but became more pronounced over time. Social stress increased the number of responses for cocaine, but did not alter the number of non-specific responses. Sex differences in self-administration were not significant. Therefore, social status appears to be a potent influence in the onset of drug taking behavior in both male and female rats.

Aggression↗
PubMed1995

Prenatal stress in rats facilitates amphetamine-induced sensitization and induces long-lasting changes in dopamine receptors in the nucleus accumbens.

Exposure of rats to restraint stress during late pregnancy produces offspring with a variety of behavioral and neurobiological alterations. It has been suggested that prenatal stress leads to long-lasting changes in the hypothalamo-pituitary-adrenal axis in the offspring. One feature of prenatally-stressed rats is a susceptibility to amphetamine self-administration. Since this behavior has been related to amphetamine-induced sensitization and the activity of the mesolimbic dopamine system, we measured dopamine receptor densities and amphetamine-induced sensitization in these animals. The motor response to the first administration of amphetamine was similar in both prestressed and unstressed groups of adult animals, but after repeated drug injections, behavioral sensitization was observed sooner in the prenatally-stressed rats than in the controls. In separate groups of adult animals, densities of D1, D2 and D3 dopamine receptor subtypes in the striatum and nucleus accumbens were measured in prenatally-stressed and control rats by quantitative autoradiography using [3H]SCH23390, [3H]sulpiride and [3H]7-OH-DPAT as ligands respectively. Prenatal stress was found to produce the following alterations in the adult offspring: (i) no significant change in D1 receptor binding in either striatum or nucleus accumbens; (ii) a significant (+24%) increase in D2 receptor binding in the nucleus accumbens; (iii) a significant decrease in D3 receptor binding in both the shell (-16%) and the core (-26%) of the nucleus accumbens. These observations indicate that prenatal stress induces long-lasting changes in the dopamine sensitivity of the nucleus accumbens and in the capacity to develop amphetamine-induced sensitization in adulthood. The possible relationship between an impaired control of corticosterone secretion in prenatally-stressed animals and long-term changes in the mesolimbic dopamine system is discussed.

Amphetamine↗
PubMed1995

[Neurobiology of dependence].

Investigations concerning dependence to drug of abuse are of pluridisciplinary nature. It is clear that to understand this complex phenomenon will not be the privilege of one particular level of psychobiological organizations. Whatever the theories, it must be stated that correlational relations exist between behavior, mental states, and brain-neuronal states whatever the transduction principles in cause. An important neglected problem to be investigated concerns the vulnerability presented by some organisms and not by other, either for the search of a drug-stimulus or to repeat the first encounter with the pharmacological agent, potentially a drug of abuse. Such vulnerability corresponds to a neurobiological state considered far from the equilibrium, i.e. homeostasis. Whether the drug, as many other agents, environmental, nutritional, sexual, tends to reduce the imbalance within the neuronal systems is a matter of debate.

Animals↗
PubMed1995

Short and long-term changes in dopamine and serotonin receptor binding sites in amphetamine-sensitized rats: a quantitative autoradiographic study.

The biochemical changes in DA and 5HT systems were investigated in amphetamine (AMPH)-sensitized rats, 1 and 15 days after cessation of treatment (5 mg/kg AMPH, i.p., twice a day for 6 days). At both times, AMPH-treated rats exhibited behavioral sensitization, as revealed by an enhancement of the stereotypic response to a challenge dose of 2 mg/Kg, ip. AMPH. Basal dopamine (DA) and serotonin (5-HT) metabolism was not significantly modified in different brain areas of AMPH-sensitized rats. Quantitative autoradiographic analysis of DA and serotonin 5-HT receptor subtypes was performed in the following brain regions: medial prefrontal cortex, nucleus accumbens, striatum, substantia nigra, ventral tegmental area, dorsal and median raphe nuclei. A significant increase of [3H]SCH 23390 binding to D1 DA receptors was observed in the substantia nigra pars reticulata 1 day but not 15 days after the cessation of AMPH treatment, whereas [3H]8-OH-DPAT binding to 5-HT1A sites was found to be significantly enhanced in the dorsal raphe nucleus at both time points. No change in D2 DA nor in 5-HT1B or 5-HT2A receptors was found in any of the brain structures examined at either time point. The obtained results suggest that DA and 5-HT systems are differently and time-dependently involved in AMPH-induced behavioral sensitization.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Social deprivation enhances the vulnerability of male Wistar rats to stressor- and amphetamine-induced behavioral sensitization.

The aim of the present study was to assess the influence of experiential factors on the vulnerability of rats to develop amphetamine (AMPH)- and stressor-induced behavioral sensitization. Young male Wistar rats with previous social experience were isolated from their peers for 2 weeks. 1) The effect of this short-lasting social deprivation were: a) a reduced tendency to explore a fearful environment; b) a prolonged exploratory activity in response to a novel but little fearful environment; and c) a dose-dependent increase in the psychomotor stimulation induced by systemic AMPH injection. 2) After repeated AMPH injections (injection every other day for 10 days), isolated rats exhibited behavioral sensitization at lower doses (0.5 and 0.75 mg/kg) than those required for group-housed rats (1 mg/kg). 3) After being submitted to a repeated stressor (3, 7 or 14 footshock sessions, with 2 days between sessions), the isolated rats exhibited a greater increase in the behavioral responsivity to a subsequent AMPH challenge (1 mg/kg) than did the group-housed rats regardless of the number of stress sessions. In conclusion, these results suggest that experiential factors such as privation of contact with peers (social isolation) may make rats more vulnerable to the long-term repercussions of chronic environmental and pharmacological challenges.

Amphetamine↗
PubMed1995

Evidence for 5-HT4 receptor subtype involvement in the enhancement of striatal dopamine release induced by serotonin: a microdialysis study in the halothane-anesthetized rat.

The present study, using the in vivo intracerebral microdialysis method, investigated the role of different serotonin receptor subtypes in the control of dopamine (DA) release exerted by serotonin (5-HT) in the striatum of halothane-anesthetized rats. Striatal dialysate DA content was reduced following the blockade of voltage-dependent Na+ channels by tetrodotoxin or by the removal of Ca2+ from the perfusion medium, and increased following depolarization with K+ ions. These findings demonstrate that under our experimental conditions, DA content reflects the neuronal origin of the neurotransmitter release. Drugs were locally applied by means of the microdialysis probe. One, 2.5 and 5 microM 5-HT significantly enhanced DA release in a concentration-dependent manner up to 157, 253 and 446% of basal values respectively. The effect induced by 1 microM 5-HT was not blocked by 10 microM (-)pindolol, a 5-HT1 receptor antagonist, 1 microM ketanserin or 10 microM cinanserin, both 5-HT2A antagonists. One or 10 microM ondansetron (GR 38032F), a selective 5-HT3 antagonist, were also ineffective. In contrast, 10 or 100 microM DAU 6285, a 5-HT3/4 antagonist, significantly reduced the effect of 5-HT on DA release (-20% and -60% respectively). Moreover, 100 microM BIMU 8, a selective 5-HT4 agonist, enhanced DA release (+85%) and this effect was reduced by 100 microM DAU 6285 (-40%). These results demonstrate that in vivo 5-HT exerts a facilitatory influence on striatal DA release and that the 5-HT4, but not the 5-HT1, 5-HT2 or 5-HT3, receptor subtype is implicated, at least partially, in this effect.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

The neonatal lesion of the meso-telencephalic dopaminergic pathway increases intrastriatal D2 receptor levels and synthesis and this effect is reversed by neonatal dopaminergic rich-graft.

The ascending dopaminergic pathway of 3-day-old rats has been unilaterally destroyed by the injection of 6-hydroxydopamine into the lateral hypothalamus. Five days later, a suspension containing embryonic dopaminergic neurones was injected in the lesioned neostriatum. Rotational responses to dopaminergic agonists were tested eight months after grafting and animals were killed one month later. Neostriatal dopaminergic D1 and D2 receptors were examined using autoradiography while changes in D2 receptor mRNA levels were studied by in situ hybridization. The lesion induced a behavioural hypersensitivity - as manifested in contralateral rotations - to dopaminergic D1 (SKF 38393) or D2 (LY 171555) agonists which was abolished by the graft. Density of D1 receptors was not affected by the lesion while D2 receptors density was increased by 20-25% in the more rostral part of the neostriatum. Changes in D2 mRNA after the lesion paralleled those observed for D2 receptor density, i.e. D2 mRNA level was increased by 15-19% in the rostral neostriatum. The graft did not influence D1 receptor densities but reversed the post-lesion increase of D2 receptors associated parameters. It is concluded that dopaminergic grafts implanted in neonatal hosts are able to normalise the density of D2 receptors by an action on their synthesis.

Animals↗
PubMed1995

Neuropeptide FLFQRFamide receptors within the ventral mesenchephalon and dopaminergic terminal areas: localization and functional antiopioid involvement.

The neuropeptide FLFQPQRF amide is a FMRFamide-like peptide with some anti-opiate properties. Neuropeptide FLFQPQRFamide receptors are present in the mammalian central nervous system and have been clearly identified as different from opiate receptors. Autoradiography has revealed neuropeptide FLFQPQRFamide receptor localization within the ventral mesencephalon, where opiate receptors are also located. In order to delineate anatomical localization of neuropeptide FLFQPQRFamide receptors, we used selective chemical lesions of dopaminergic cells and intrinsic perikarya of the ventral mesencephalon, coupled with in vitro autoradiographic techniques. We show that: (i) unilateral lesions of dopaminergic perikarya produced by 6-hydroxydopamine did not affect either ipsi or contralateral neuropeptide FLFQPQRFamide receptor density within the mesencephalon; (ii) unilateral lesions of intrinsic perikarya by ibotenic acid injected into the ventral tegmental area produced a significant reduction of neuropeptide FLFQPQRFamide receptors (40%) in this region; (iii) in the substantia nigra pars compacta, ibotenic acid unilateral lesions did not affect the density of neuropeptide FLFQPQRF-amide receptors; (iv) unilateral 6-hydroxydopamine or ibotenic acid lesions failed to affect neuropeptide FLFQPQRFamide binding in the dopaminergic projection areas. These results suggest that, like opiate receptors, the neuropeptide FLFQPQRFamide binding sites are not localized on dopaminergic neurons but are distributed on both soma of non dopaminergic cells in the ventral tegmental area and on fibers afferent to the ventral tegmental area and substantia nigra pars compacta. To evaluate the possibility that the stimulation of neuropeptide FLFQPQRFamide receptors may affect the opioid modulation of mesocorticolimbic dopaminergic neuron activity, we tested the effects of neuropeptide FLFQPQRFamide ventral tegmental area infusion (0.25-10 micrograms) on the behavioral activation induced by intra-ventral tegmental area morphine infusion. We observed that in the ventral tegmental area, the stimulation of neuropeptide FLFQPQRFamide receptors inhibits morphine-induced locomotor hyperactivity. These results suggest that in the ventral tegmental area, neuropeptide FLFQPQRFamide may participate, via an indirect mechanism, to the control of the mesocorticolimbic dopaminergic system activity by counteracting the effect of opioids.

Animals↗
PubMed1995

Paw preference and brain dopamine asymmetries.

The hemispheric content of dopamine and its metabolites in the frontal cortex, caudatus putamen and nucleus accumbens septi was evaluated in relation to behavioral lateralization assessed by paw preference. Three groups of C3H/He mice were selected on the basis of their performance in the paw preference test (left-handed, ambidextrous and right-handed) and levels of dopamine and its metabolites were measured in the two hemispheres of each group. Mice showed significant differences in hemispheric content of dopamine and 3-4 dihydroxyphenylacetic acid in the nucleus accumbens septi depending on the behavioral lateralization as expressed by paw preference. The hemispheric dominance (right hemisphere/right hemisphere + left hemisphere content of dopamine and metabolites x 100) was also calculated for each mouse. Significant differences in hemispheric dominance for dopamine, 3-4 dihydroxyphenylacetic acid and 3-methoxytyramine in the nucleus accumbens were found between right-handed and left-handed mice. This dominance was ipsilateral to the preferred paw: % right hemisphere/total content of dopamine and its metabolites were lowest in left-handed, highest in right-handed and intermediate in ambidextrous mice. Finally, individual % right hemisphere/total content for dopamine, 3-4 dihydroxyphenylacetic acid and 3-methoxytyramine in the nucleus accumbens positively correlated with individual paw preference scores. The analysis of the other brain areas did not reveal any significant effect. These results suggest a strong relationship between mesoaccumbens dopamine asymmetries and both the direction and the intensity of behavioral lateralization as expressed by paw preference in mice.

3,4-Dihydroxyphenylacetic Acid↗