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  • 1
    ISSN: 1432-1106
    Keywords: Parataenial nucleus ; Nucleus accumbens ; Autoradiography ; Thalamus ; Limbic system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
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  • 2
    ISSN: 1432-2072
    Keywords: Behaviour ; Morphine ; Naloxone ; Withdrawal syndrome ; Ethopharmacology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The intensity of opiate withdrawal syndrome in rats is usually quantified on the basis of selected physical signs or global scores. However, the selection criteria of signs and scores have not been subjected to an ethological discussion, hence they appear to be somewhat arbitrary. The objectives of this study were thus: i) to analyse the rat's behaviour during the nalox-one-precipitated morphine withdrawal syndrome, ii) to evaluate the validity of classic methods, and iii) to design a new “etho-score”. Ten rats were implanted with morphine pellets (75 mg×2, SC), all receiving different naloxone doses following a within-subject design (0, 0.01, 0.05, 0.1, 0.5, 1 mg/kg SC). Twenty unexperienced rats and 20 with placebo pellets were injected with either saline or naloxone. Behaviour was videotaped and later analysed by computer-based ethological techniques. The ethogram encompassed 16 patterns displayed by rats during morphine withdrawal. Frequency, duration and latency of each pattern was measured, and a cluster analysis allowed discerning the structure of behaviour. Several physical signs and the Gellert-Holtzman score were also evaluated. The data revealed that writhing responses linearly changed in a dose-related fashion, and mastication was also enhanced after naloxone. Wet-dog shakes and jumping changed following an U-shaped curve. Significant changes in weight loss were found to be dose-dependent, and highly correlated to diarrhea. Learning effects were found to reliably affect exploration, writhing responses and some physical signs. The Gellert-Holtzman score was gradually enhanced after naloxone, being affected by learning as well. Naloxone affected lying and self-care responses in placebo rats. To sum up, the data indicated that: i) classic signs are useful, although most of them are disrupted by high naloxone or affected by learning effects, ii) the Gellert-Holtzman score was validated in this study, and iii) mastication and weight loss are good indicators of naloxone-precipitated morphine withdrawal, representing the basis of an “etho-score” which is herein proposed.
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  • 3
    Electronic Resource
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    Springer
    Psychopharmacology 149 (2000), S. 115-120 
    ISSN: 1432-2072
    Keywords: Key words Opiate ; Withdrawal ; Place aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Administration of low doses of opiate antagonists to morphine-dependent rats produces an aversive response as measured by a conditioned place aversion, but the time course of such a learned aversion is largely unknown. Objectives: The purpose of this experiment was to examine the time course for the expression of a place aversion to opiate withdrawal. Methods: Morphine-dependent rats were tested in a three-chamber place- aversion apparatus. The conditioning phase consisted of three pairings of either naloxone (15 µg/kg s.c.) or vehicle with two compartments, with the most similar time allotments during the preconditioning test. During the testing phase, rats were again allowed to explore the entire apparatus. Different groups were tested at 24 h, 1 week, 2 weeks, 4 weeks, 8 weeks, and 16 weeks post-conditioning (morphine-free tests). Results: A robust place aversion was recorded at every time point tested, including at 16 weeks. In previously published work, placebo-pelleted rats tested with naloxone at the same dose failed to show a place aversion and nondependent rats showed a stable lack of aversion at tests up to 56 days. Dependent animals without naloxone also failed to show a place aversion at any of those time points. Conclusions: In the absence of any active intervention, the place aversion produced by opiate withdrawal is very long lasting and provides a model for protracted abstinence that may be useful for delineating the neurobiological substrate for vulnerability to relapse.
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  • 4
    ISSN: 1432-2072
    Keywords: Substance P ; Ventral mesencephalon ; Investigatory behavior ; Motor behavior ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 μg) 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 μg) was similar to that elicited by VTA infusions, with the exception that center rearing was not enhanced. SP administration into cortex (3 μg) 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.
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  • 5
    ISSN: 1432-2072
    Keywords: Neurotensin ; Ventral mesencephalon ; Investigatory behaviour ; Motor behavior ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 μg) 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.
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  • 6
    ISSN: 1432-2072
    Keywords: Amphetamine ; Apomorphine ; Dopamine ; Exploration ; Locomotor activity ; Hole-board ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
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  • 7
    ISSN: 1432-2072
    Keywords: Self-stimulation ; Area ventralis tegmenti ; Lateral hypothalamus ; Reserpine ; Tyrosine hydroxylase inhibition ; Dopamine Β-hydroxylase inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioral effects of low doses of the catecholamine (CA) synthesis inhibitor, α-methyl-p-tyrosine (α-MPT, 50 mg/kg i.p.), or the norepinephrine (NE) synthesis inhibitors (FLA-63, 15 mg/kg i.p., U-14624, 50 mg/kg i.p., or disulfiram, 150 mg/kg i.p.) were studied in rats pretreated with reserpine (1 mg/kg i.p.) 24 h before. Rats were implanted either in the area ventralis tegmenti (AVT) or in the lateral hypothalamus (LH). The modifications of CA synthesis and endogenous CA levels were estimated in a parallel experiment. Reserpine treatment produced a slow decrease in self-stimulation (SS) rates during the first 12 h; SS rates were 85% of control values 24 h after reserpine treatment. Injection of α-MPT in reserpine-pretreated rats inhibited SS (85% decrease 3 h after administration either in AVT or LH rats), whereas dopamine Β-hydroxylase inhibition had no great effect on SS. The administration of very low doses of α-MPT (20 mg/kg i.p.) to rats treated with reserpine (24 h before) plus FLA-63 (1 h before) induced an important decrease in SS rates in AVT-implanted rats only. The major conclusion is that dopaminergic neurons seem to be involved in AVT and LH SS. The last experiment suggests the involvement of a balance between dopaminergic and noradrenergic neurons in AVT SS.
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  • 8
    ISSN: 1432-2072
    Keywords: Arginine vasotocin ; Melatonin ; Exploration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 μg) 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 producted 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.
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  • 9
    ISSN: 1432-2072
    Keywords: Opiates ; Nucleus accumbens ; Supersensitivity ; Chronic neuroleptic ; 6-OHDA lesion ; Mesolimbic dopamine neurones ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
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  • 10
    ISSN: 1432-2072
    Keywords: Enkephalin ; Ventral mesencephalon ; Investigatory behaviour ; Motor behaviour ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mesolimbic dopamine (DA) system, originating in the ventral tegmental area and projecting to limbic forebrain regions, plays a crucial role in mediating several important aspects of behaviour. Proximal to these DA neurons are enkephalin-containing nerve fibers. In an attempt to characterize the behavioural role of enkephalinergic transmission in the VTA, the present experiment examined in detail the investigatory and motor responses to microinfusion of d-ala-met-enkephalin (DALA), a long lasting analogue of enkephalin, into the ventral tegmental area (VTA). Injections into the substantia nigra (SN) and the hippocampus (HPC) were also performed as controls for site specificity. The behavioural apparatus consisted of an eight-hole box monitored by a video camera. Four doses of DALA were injected in the VTA (0.05, 0.1, 1 and 2.5 μg/μl bilaterally in 1 μl volume) and one dose in the SN and HPC (0.1 μg/μl bilaterally in 1 μl volume). The effect of DALA injections in the VTA was characterized by an inverted U-shape dose-effect curve. The low doses (0.05 and 0.1) induced an increase in the frequency of hole visits accompanied by a decrease in the mean duration of visits, whereas the highest doses induced a decrease in hole visit frequency. Low doses of DALA had no effect on strategy or organization of exploration, whereas the high doses produced decreased switching between holes. After low doses of DALA, locomotor activity at the periphery of the testing box was not significantly affected but locomotor activity in the centre was increased. After high doses of DALA, locomotor activity in the center and at the periphery of the box were decreased. Frequency of rearing was either not affected or decreased by DALA treatment. DALA injected in the SN resulted in a small increase in frequency of hole visits and did not affect rearing and locomotor activity. DALA injection in the HPC had no effect on investigatory and spontaneous motor behaviour. The results are discussed in terms of a modulatory role of endogenous enkephalin on mesolimbic dopamine neurons.
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