Biomedical subjects

L Stinus

Publications and source records attributed to L Stinus.

At least 73 records · Page 4Linked to original sources

PubMed1986

Amphetamine, apomorphine and investigatory behavior in the rat: analysis of the structure and pattern of responses.

In the present experiments, the effects of a wide range of doses of d-amphetamine and apomorphine were studied on investigatory behavior in an automated eight-hole box. Amphetamine (0.125, 0.25, 0.5, 1.0, 3.0, 5.0 mg/kg) increased frequency and total duration of responses, and decreased mean duration in a dose-dependent manner. The strategy and organization of responses, as measured by the order of hole-visits and hole-switching, were unchanged at lower doses of amphetamine but were altered at higher doses. Perseverative hole-poking was observed at the highest dose (5.0) as indicated by increased number of hole-pokes per hole-visit. Apomorphine (0.05, 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 mg/kg) decreased mean duration of responses, but in contrast to amphetamine markedly diminished frequency. Locomotor activity was also measured at all doses of both drugs. Our observations indicate that these two stimulant drugs both of which increase motor activity, have markedly different effects on investigatory responses. It is likely that amphetamine increases prepotent response tendencies (i.e., hole-poking), although this does not necessarily reflect enhanced exploration. Further, the results obtained with amphetamine support predictions made by the Lyon-Robbins behavioral theory of amphetamine effects.

Amphetamine↗

PubMed1986

Chronic treatment with five different neuroleptics elicits behavioral supersensitivity to opiate infusion into the nucleus accumbens.

It has previously been demonstrated that direct opiate infusion into nucleus accumbens elicits psychomotor activation in rats. In the present study, the effects of chronic treatment with five different neuroleptics on this behavioral response were investigated. All neuroleptics tested (haloperidol, sulpiride, flupentixol decanoate, perphenazine enanthate, fluphenazine decanoate, palmitic ester of pipotiazine) induced a marked behavioral supersensitivity to intraaccumbens opiate infusion. A similarly enhanced sensitivity was observed in chronic reserpine-treated rats. The maximum sensitivity to opiates appeared 2-3 weeks after the beginning of neuroleptic treatment and was present up to 1 month after the end of treatment. Naloxone blocked the neuroleptic-induced enhanced response to opiates. It is concluded that chronic blockade of dopaminergic transmission results in considerable functional alterations of the endogenous opiate systems. The results are discussed in terms of possible underlying neuronal mechanisms, and important clinical implications are noted.

Animals↗

PubMed1986

Ventral tegmental area infusion of substance P, neurotensin and enkephalin: differential effects on feeding behavior.

The neuropeptides substance P, neurotensin and [Met]enkephalin are found in the ventral tegmental area, site of the A10 dopamine cell bodies. Evidence suggests a functional interaction between these peptides and the dopaminergic neurons. All three peptides have been shown to exert an activating effect on these neurons. The present study analyzed the effects of ventral tegmental area infusion of neurotensin, substance P and D-ala-[Met]enkephalin on feeding behavior. These effects were studied in both food-deprived and satiated rats. During a 30 min test, the following parameters were registered: latency to eat, total food intake, food spillage, number of eating bouts and duration of eating. Similar measures were taken for drinking. In deprived rats substance P (0.5, 3.0 micrograms) increased latency to eat but did not affect other parameters, and substance P did not affect eating in satiated rats. Neurotensin (0.5, 2.5 micrograms) increased latency to eat and markedly reduced food consumption in deprived rats and had no effect in satiated rats. D-Ala-[Met]enkephalin (0.1, 1.0 micrograms) stimulated feeding behavior in both deprived and satiated rats. These results show that although the different peptides are presumed to activate the dopaminergic A10 neurons, their effects on feeding behavior can be differentiated. The findings are discussed in terms of motor and motivational mechanisms, and the relative contributions of specific and non-specific influences on feeding are considered.

Animals↗

PubMed1985

A novel long-lasting dopamine receptor blocker: haloperidol-bovine serum albumin conjugate.

The present study was undertaken in order to develop a long-lasting antagonist of dopamine receptors with a technique applicable to other molecules. Haloperidol was immobilized on a macromolecular backbone (bovine serum albumin) with a coupling ratio of 14 molecules haloperidol per molecule of bovine serum albumin. The long-lasting blockade of dopamine receptor activity was evaluated with the d-amphetamine-induced rotation model in rats. Unilateral intracerebral infusion of the conjugate into the caudate nucleus induced a blockade of dopamine receptors which lasted more than six days. The conjugate was able to trigger a greater amphetamine-induced rotation rate then haloperidol alone. This ipsilateral rotation appeared after doses of conjugate lower than those needed for unilateral haloperidol intracaudate infusion. This compound will enable the reversible blockade of dopaminergic transmission in a restricted area of the brain (diffusion of the conjugate was studied in detail) over a period of time needed for a behavioural study without the drawbacks of chemical or mechanical lesions.

Animals↗

PubMed1985

Behavioral analysis of the effect of substance P injected into the ventral mesencephalon on investigatory and spontaneous motor behavior in the rat.

In the present experiments the behavioral response to substance P (SP) microinfusion into the ventral tegmental area (VTA), substantia nigra (SN), and sensorimotor cortex (CX) was investigated in detail. The experiments were carried out using an eight-hole box to measure exploratory behavior and a video monitor for the analysis of spontaneous motor behavior. When infused into the VTA, SP (0.125, 0.5, 3.0 micrograms) augmented the frequency and total duration of hole-pokes, and tended to diminish the mean duration of hole-pokes. The strategy and organization of responses, as measured by the order of hole-visits and hole-switching, were unchanged by SP and there was no indication of stereotypy, measured by the number of hole-pokes per hole-visit. The open-field analysis revealed a marked increase in locomotion and rearing, both in the periphery and center of the arena; grooming was decreased by SP. The behavioral profile following SN infusions of SP (3.0 micrograms) was similar to that elicited by VTA infusions, with the exception that center rearing was not enhanced. SP administration into cortex (3 micrograms) had no significant effect on any behavioral measures. It is hypothesized that SP infused into the ventral mesencephalon results in an enhancement of approach response tendencies, suggesting that endogenous SP in this region may regulate spontaneous behavior. The possibility of an interaction between SP and meso-telencephalic dopamine neurons is discussed.

Animals↗

PubMed1985

Chronic neuroleptic treatment and mesolimbic dopamine denervation induce behavioural supersensitivity to opiates.

In the present study the functional relationship between enkephalinergic and dopaminergic neurones at the level of the nucleus accumbens was investigated. The study consisted of two experiments in which dopaminergic (DA) transmission was chronically inhibited, and the behavioural locomotor response to intra-accumbens opiate injections analysed. First, specific 6-OHDA lesion of the DA-A10 neurones (either in nucleus accumbens or ventral tegmental area) was found markedly to increase the behavioural excitatory effects induced by nucleus accumbens injection of opioid peptides or morphine. Specific lesion of the central noradrenergic neurones had no such effect. Second, chronic pharmacological blockade of DA activity either with reserpine or a neuroleptic (pipothiazine palmitate) similarly induced a strong enhancement of the behavioral response to intra-accumbens opiate injection. The results are discussed in terms of novel mechanisms underlying denervation supersensitivity, and may have important implications for the relation between dopamine dysfunction in mental illness and opiate addiction.

Animals↗

PubMed1985

Behavioral analysis of the effect of neurotensin injected into the ventral mesencephalon on investigatory and spontaneous motor behavior in the rat.

The present experiments examined in detail the behavioral response to microinfusions of neurotensin (NT) into the ventral tegmental area (VTA), substantia nigra (SN) and hippocampus (HPC). The behavioral apparatus consisted of an eight-hole box in which investigatory and spontaneous motor behavior were recorded. Three doses (0.175, 0.5, 4.0 micrograms) of NT were injected into the VTA. The main effect of NT was a strong augmentation of rearing (frequency and duration) both in the periphery and center of the arena, accompanied by a small increase in locomotion and decreased grooming. NT had no effect on the strategy, organization, or duration of exploration but did augment frequency of hole visits towards the end of the session. NT injected into the SN and HPC had no effect on investigatory and spontaneous behavior with the exception of an increase in peripheral locomotion after HPC-NT injections. The results are discussed in terms of a modulatory role of endogenous NT on mesolimbic dopamine neurons.

Animals↗

PubMed1985

Disappearance of hoarding behavior after 6-hydroxydopamine lesions of the mesolimbic dopamine neurons and its reinstatement with L-dopa.

The consequences of 6-hydroxydopamine lesions of the mesolimbic dopamine system on hoarding behavior were investigated in the rat. Specific lesions of this system, at the level of either the ventral tegmental area or the nucleus accumbens, resulted in abolition or severe reduction of hoarding activity. Similar lesions of the forebrain noradrenaline neurons did not affect hoarding. In further experiments, amphetamine and apomorphine locomotor responses, spontaneous motor behavior, food intake and eating patterns, and the existence of any regulatory deficits were examined. A subtle disorganization of eating patterns was found in animals with mesolimbic-dopamine lesions. It was determined that the hoarding deficit could not be due to motor, ingestive, or regulatory impairments. In a final experiment, it was demonstrated that hoarding behavior can be restored to control levels in dopamine-lesion rats by prior treatment with the catecholamine presursor L-dopa. These findings suggest that hoarding activity is mediated by mesolimbic dopamine neurons, and it is hypothesized that this system is necessary for the facilitation of certain types of foraging responses under a high level of arousal.

Animals↗

PubMed1984

The distribution of the projection from the parataenial nucleus of the thalamus to the nucleus accumbens in the rat: an autoradiographic study.

In this study the intrastriatal distribution of afferents arising from the parataenial nucleus of the thalamus was investigated. Tritiated leucine and proline injected into the parataenial nucleus was found to densely label the entire anterior-posterior extent of the medial nucleus accumbens. The projection was for the most part limited to this striatal subregion, although some moderate labelling was found along the medial wall of the anterior caudateputamen . The terminal labelling within accumbens was characterized by a distinct patchiness . Other efferent connections of the parataenial nucleus observed in this study include the thalamic reticular nucleus, the basolateral and central nuclei of the amygdala, the septum, the medial frontal cortex, the entorhinal cortex and subiculum. This projection is distributed to the "limbic afferented " sector of striatum, and there is a nearly complete overlap between the parataenial afferents and those coming from hippocampus. The present findings suggest that the parataenial nucleus is an important thalamic link between limbic and striatal processing.

Afferent Pathways↗

PubMed1984

Repeated stress increases locomotor response to amphetamine.

Adult male rats submitted to mild, 20 min electric foot shock sessions for 10 days displayed an enhanced locomotor response to 0.75 mg/kg (+)amphetamine 24 h after the last shock session, when compared to non-stressed controls. This effect was still present in rats specifically deprived of their forebrain noradrenergic innervation, suggesting the involvement of a dopaminergic mechanism. Cortical and limbic dopamine turnover which increased immediately after acute and repeated foot shocks returned to normal 24 h later, at the time of the pharmacological testing. This fact indicates that a permanent modification of the basal DA activity is not responsible for the above effect of stress. Locomotor hyperactivity produced by 0.6 mg/kg apomorphine was enhanced in experimental animals, while hypoactivity resulting from the injection of 0.05 mg/kg apomorphine was similar in control and shocked rats. This latter result suggests the existence of an increased postsynaptic DA sensitivity as a result of repeated stress.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1983

Changes in cortical and subcortical levels of monoamines and their metabolites following unilateral ventrolateral cortical lesions in the rat.

Suction lesions were made in the anterior, posterior or both halves of the right ventrolateral cortex in rats. Six days later, levels of the monoamine neurotransmitters, norepinephrine (NE), dopamine (DA) and serotonin (5-HT), and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), were measured in cortical and subcortical regions of lesioned rats and compared to values in sham-operated animals. NE and 5-HT were decreased in sections of ipsilateral (right) cortex including, and posterior to lesions, while 5-HIAA was increased throughout the ipsilateral cortex. Decreases in monoamines and increases in metabolites and metabolite:monoamine ratios (especially 5-HIAA:5-HT) were found in ipsilateral subcortical structures, including striatum, nucleus accumbens, hippocampus, hypothalamus, midbrain and brainstem, depending on the type of lesion. Subacutely, focal ventrolateral cortical lesions may profoundly alter the levels and utilization rates of monoamine neurotransmitters in widespread regions of the ipsilateral hemisphere.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1983

Effect of injections of 6-OHDA into either nucleus accumbens septi or frontal cortex on spontaneous and drug-induced activity.

The effect of injections of 6-hydroxydopamine (6-OHDA) into either frontal cortex (FCx) or nucleus accumbens (NAS) on spontaneous, amphetamine and apomorphine photocell cage activity was studied. Both lesions groups had significant noradrenaline depletion in frontal cortex but only the FCx group had significant dopamine depletion in frontal cortex. Whereas NAS 6-OHDA rats exhibited enhanced apomorphine- and decreased amphetamine-activity there were no differences in activity of the FCx group. 6-OHDA NAS rats also exhibited spontaneous hypoactivity on the third but not the seventh post-operative day; there were no differences in spontaneous activity on either days in the FCx group. In 1975 Kelly, Seviour and Iversen demonstrated that destruction of forebrain dopaminergic terminals induced with injection sof 6-hydroxydopamine (6-OHDA) into the nucleus accumbens septi (NAS) attenuated the locomotor response to 1.5 mg/kg d-amphetamine without affecting stereotypy seen at 5.0 mg/kg. In addition, these rats exhibited an enhanced locomotor response to the dopamine receptor agonist apomorphine, an effect thought to reflect receptor supersensitivity induced by dopamine denervation (Ungerstedt, 1971). Biochemical assay data revealed that dopamine levels were significantly reduced both in nucleus accumbens septi (NAS) and olfactory tubercle (OT) but not neostriatum; thus it was concluded that amphetamine- and apomorphine-induced locomotor activity is mediated by the mesolimbic dopamine system. Since then it has become clear that the A10 group of dopamine (DA) cells bodies in the ventral tegmental area (VTA), give rise to dopamine fibres which innervate not only NAS and OT, but also frontal cortex (Bjorklund and Lindvall, 1978).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

The cytology of dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental area of the rat: a light- and electron-microscopic study.

The results of this study support the conclusion that dopaminergic cells can be distinguished from non-dopaminergic cells, at both the light- and electron-microscopic level, by cytological features, and particularly by the pattern of Nissl substance. In both the substantia nigra and the ventral tegmental area, two main categories of cell type can be identified in Nissl preparations: (1) dark-staining, basophilic cells with large masses of Nissl substance and (2) light-staining cells with more translucent cytoplasm. The following findings provide evidence that the basophilic cells of both substantia nigra and ventral tegmental area are the dopaminergic cells. (1) There is a good correlation between the topographic distribution of basophilic cells and that of dopaminergic cells mapped by both histofluorescence and immunohistochemical methods. (2) After unilateral destruction of the dopaminergic neurons by intracerebral injection of 6-hydroxydopamine in the dopaminergic pathway, the basophilic cells in the substantia nigra and ventral tegmental area disappeared on the lesion side, while the lighter-staining cells appeared unaffected. (3) In normal rats, and in rats with unilateral 6-hydroxydopamine lesions, intraventricular injection of [3H]norepinephrine was used for specific labeling of dopaminergic neurons. In autoradiograms of semithin sections, such labeling was observed only in dark-staining and not in light-staining cells, and in cases of unilateral 6-hydroxydopamine lesion was totally absent on the lesion side. Electron-microscopy showed much of the cytoplasm of the basophilic dopaminergic cells to be densely filled with free ribosomes associated with large, well organized complexes of rough endoplasmic reticulum. The cytoplasm of the light, non-dopaminergic cells contains only sparse free ribosomes and small, widely spaced aggregates of rough endoplasmic reticulum. Both cell types occur in a similar variety of size and shape.

Animals↗

PubMed1982

Central administration of arginine vasotocin: effects on exploratory behavior in the rat.

Synthetic arginine vasotocin (AVT) was infused into rat brains either by intraventricular administration or by local infusion on the pineal body. Subsequently, exploratory behavior was analyzed in a hole board. The behavioral effects induced by this peptide were dependent on the time of day, i. e. the light or the dark phase. High intraventricular doses (0.4 microgram) administered during the light phase altered exploratory activity such that the number of hole visits was increased, while the duration of each visit was decreased; lower doses produced no effect. In contrast, during the dark phase peripineal infusion of AVT (10(-4) pg) attenuated the number of hole visits and increased the mean duration of the visits. The strongest effects were obtained with peripineal applications during the dark phase. This treatment also resulted in significantly lowered levels of pineal melatonin.

Animals↗

PubMed1982

GABAergic mechanisms within the ventral tegmental area: involvement of dopaminergic (A 10) and non-dopaminergic neurones.

The spontaneous activity of rats was measured after activation or inhibition of GABA activity in the ventral tegmental area of the midbrain (VTA). Six hours after bilateral injection of ethanolamine-o-sulphate (GABA agonist) into the VTA, the behavioural activation induced either by d-amphetamine (amph) or by bilateral VTA infusion of a long-lasting enkephalin analogue was completely blocked. Bilateral infusion of picrotoxin (GABA antagonist) into the VTA elicited a short-lived (40 min) dose-dependent behavioural activation which was not reduced either by prior specific lesion of the meso-cortico-limbic dopaminergic neurones or by administration of the opiate antagonist naloxone. Moreover, the simultaneous administration of picrotoxin and amph induced complex changes in behaviour which consisted of additive effects during the first 40 min, followed by an inhibition of the activating effect of amph. Our findings indicate that GABA-mediated inhibition involves both dopaminergic and non-dopaminergic neurones within the VTA, and possible implications for human pathology are discussed.

Animals↗

PubMed1981

Hyperactivity and hypoactivity produced by lesions to the mesolimbic dopamine system.

Spontaneous locomotor activity and the locomotor response to amphetamine and apomorphine were studied in rats subjected to either radiofrequency (RF), 6-hydroxydopamine (6-OHDA) or both RF and 6-OHDA lesions of the mesolimbic dopamine (DA) system. Large 6-OHDA lesions of the ventral tegmental area (VTA) or of the nucleus accumbens (N.Acc.) produced hypo-activity in the open field, a complete blockade of the locomotor stimulating effects of D-amphetamine and a profound supersensitive response to apomorphine as measured by a significant increase in locomotor activity as compared to sham-operated animals. In contrast, smaller 6-OHDA lesions of the VTA produced significant increases in spontaneous daytime and nocturnal activity with the biggest effect occurring at the lowest dose. RF lesions to the VTA produced even greater hyperactivity which was blocked by the addition of a 6-OHDA lesion to the N.Acc. The rats with RF lesions to VTA alone that were spontaneously hyperactive remained hyperactive after injection of amphetamine, whereas apomorphine produced a significant decrease in this hyperactivity. In contrast, the rats with the combined RF lesion and N.Acc. 6-OHDA lesion showed a blockade of the locomotor stimulating effects of D-amphetamine and a potentiated response to apomorphine identical to that observed with a N.Acc. lesion alone. All lesion groups revealed massive depletion of DA in the N.Acc. and anterior striatum with significantly greater depletions in those groups showing hypoactivity and hypo-responsiveness to amphetamine. All groups except the N.Acc. 6-OHDA alone group showed significant depletions of DA in the posterior striatum. Thus, limited destruction of the mesolimbic DA system can produce hyperactivity, but more extensive destruction of this system in the region of the N.Acc. and anterior striatum can reverse this hyperactivity and produce a hypo-responsiveness to the locomotor stimulating effects of amphetamine. These results suggest an essential role for dopamine in the expression of spontaneous and stimulant-induced activity. Furthermore, the much larger increase in spontaneous activity in the RF-VTA lesion group as compared to the VTA-6-OHDA groups suggests the presence of an, as yet unidentified, powerful inhibitory influence to the mesolimbic DA system within the midbrain tegmentum.

Animals↗

PubMed1980

[Effects of lesions of the anterior raphe nuclei on the self-administration of d-amphetamine in the rat : considerable increase of desire for the poison].

The acquisition of the intravenous self-administration of d-amphetamine was studied after separate lesions of anterior raphe nuclei (dorsal or median). Every lever-press delivered 2.5 microliter of a d-amphetamine solution dosed at 7.5 microgram/kg. Lesion of anterior raphe nuclei produced an hyper-sensitivity to d-amphetamine as indicated by a dramatic increase in self-administration by experimental Rats compared to the controls. Moreover this enhanced self-administration behavior is observed with a low blood concentration of d-amphetamine. The greater increase was obtained for median raphe lesioned Rats. These effects are interpreted in terms of 5HT-DA balance and could provide an experimental model for neurobiological bases of drug addiction studies.

Animals↗

PubMed1980

Locomotor hyperactivity and hypoexploration after lesion of the dopaminergic-A10 area in the ventral mesencephalic tegmentum (VMT) of rats.

The lesion of the ventral mesencephalic tegmentum (VMT) and especially of the dopaminergic (DA) A10 neurons induced disturbances of spontaneous activity in the rat. Measured in different situations (circular corridor, open field, hole box), locomotor activity was dramatically and permanently increased (5 days of recording) without modifications of the circadian rhythm, although exploratory patterns of behavior were reduced. In contrast, the administration of a low dose of D-amphetamine (1 and 2 mg/kg i.p.) to naïve rats induced an increase of both locomotor and exploratory activities. A qualitative analysis of spontaneous activity of rats after VMT lesions and after administration of D-amph, revealed opposing aspects of behavior. Residual response to D-amph of VMT-lesioned rats suggest a subtotal destruction of DA-A10 neurons, the implication of an over activity of these remaining DA-A10 neurons on behavioral deficit is considered. Our results can be explained by a deficiency in attention processes.

Animals↗