The repeated administration of addictive drugs, such as amphetamine, cocaine, and morphine, produces a progressive enhancement (sensitization) of their psychomotor activating effects. We have ...previously shown that administration of amphetamine or cocaine in a distinct test environment promotes more robust psychomotor sensitization than if they are given at home. No information is available, however, on whether this environmental manipulation has a similar effect on sensitization to morphine, a drug that enhances dopamine (DA) release in the striatum indirectly by disinhibiting midbrain DA neurons.
The main goal of present study was to determine whether exposure to a distinct environmental context facilitates morphine sensitization.
As an index of psychomotor activation, we used rotational behavior in rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal DA system. There are inconsistencies in the literature regarding the ability of morphine to elicit rotational behavior. Therefore, in experiment 1 we determined the effect of 2.0, 3.0, 4.0, 6.0, and 8.0 mg/kg, IP, of morphine on rotational behavior. In experiment 2, we studied the effect of five consecutive IV infusions of saline or morphine (2.0 mg/kg) in rats treated either in their home cage or in a distinct and relatively novel test environment. After 5 days of withdrawal, all rats received an IV infusion of 2.0 mg/kg morphine (Morphine challenge). The following day all rats received an IV infusion of saline (Saline challenge).
Morphine produced a dose-dependent increase in rotational behavior. Environmental novelty enhanced both the acute psychomotor response to morphine and its ability to induce psychomotor sensitization. Furthermore, a conditioned rotational response was seen only in animals treated in the novel environment.
Environmental novelty can facilitate the development of sensitization to the psychomotor activating effects of major addictive drugs, such as amphetamine, cocaine, and morphine.
The present study aimed to test the hypothesis that mice lacking the MCHR1 receptor (Melanin-Concentrating Hormone Receptor-1) present an elevated vulnerability towards the neurobehavioural effects ...of
d-amphetamine, presumably due to previously established up-regulations of dopamine D1 receptors in these mice. We examined the psychomotor effects of five once-daily injections of 1.5 and 3 mg/kg
d-amphetamine (i.p.) or ten once-daily injections of 2.25 mg/kg
d-amphetamine in knockout (KO) mice lacking the MCHR1 receptor. The first injection of
d-amphetamine induced a greater psychomotor response amongst the KO mice at 2.25 and 3.0 mg/kg. On all subsequent
d-amphetamine injections, KO mice still showed greater levels of psychomotor activity than the WT mice, but with no between-genotype difference in the rate of development of sensitization (similar slopes of the curves). Furthermore, 24 h after the last injection of 2.25 mg/kg
d-amphetamine both genotypes exhibited a significant post-sensitization conditioned activity. Thus, MCHR1 receptors are likely not deeply involved in the mechanisms of induction of sensitization and related conditioned activity induced by
d-amphetamine, albeit our results confirm a contribution of these receptors to the mechanisms of the acute effects of that drug, possibly via an inhibitory action on the dopaminergic mesolimbic system. Our results do not support the hypothesis of a functional contribution of MCHR1 receptors to the addictive effects of
d-amphetamine.
We have previously shown that environmental novelty can potentiate the activating effects of morphine and the development of sensitization to this effect. OBJECTIVES. Our main goal was to determine ...whether environmental novelty can also modulate the prophagic (time spent eating and food intake; experiment 1) and/or the analgesic (tail-flick test; experiments 2 and 3) effect of morphine, as well as the development of tolerance or sensitization to these effects.
In experiment 1, two groups of rats were administered seven intraperitoneal (i.p.) injections of either saline or morphine (4.0 mg/kg) either in their home cages (home groups) or in a distinct environment (novelty groups). After 7 days of withdrawal, both groups underwent a morphine challenge (4.0 mg/kg, i.p.). In experiment 2, home and novelty rats were administered four doses of morphine (0.0, 2.0, 4.0, and 8.0 mg/kg, i.p.) following a counterbalanced order. In experiment 3, home and novelty rats were administered eight intraperitoneal (i.p.) injections of either saline or morphine (8.0 mg/kg) and then given a morphine challenge (4.0 mg/kg).
Environmental novelty enhanced the locomotor activating effect of morphine and the expression of sensitization to this effect (even after a period of withdrawal). Environmental novelty had relatively little effect on morphine-induced eating, and no effect on morphine-induced analgesia.
Environmental context can have very different consequences on distinct drug effects as well as on distinct neurobehavioral adaptations to the same drug treatment (e.g., psychomotor sensitization versus analgesic tolerance).
Cocaine's ability to interact with σ receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel σ receptor ligands with antagonist activity were evaluated ...in Swiss Webster mice: BD1018 (3
S-1-2-(3,4-dichlorophenyl)ethyl-1,4-diazabicyclo4.3.0nonane), BD1063 (1-2-(3,4-dichlorophenyl)ethyl-4-methylpiperazine), and LR132 (1
R,2
S-(+)-
cis-
N-2-(3,4-dichlorophenyl)ethyl-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for σ
1 receptors. The three compounds vary in their affinities for σ
2 receptors and exhibit negligible affinities for dopamine, opioid, GABA
A and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized σ receptor agonist di-
o-tolylguanidine (DTG) and the novel σ receptor agonist BD1031 (3
R-1-2-(3,4-dichlorophenyl)ethyl-1,4-diazabicyclo4.3.0nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of σ receptors, an antisense oligodeoxynucleotide against σ
1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of σ receptors is capable of attenuating a number of cocaine-induced behaviors.
The investigation was aimed at investigating whether the dopaminergic projection arriving at the nucleus septi lateralis (NSL) is involved in the facilitatory effect of vasopressin (AVP) on memory ...retrieval. The bilateral 6-OHDA lesions to the NSL were made in 20 male Wistar rats before testing the intracerebroventricular (i.c.v.) AVP injection on recall in a passive avoidance situation. Eighteen additional rats served as sham-operated controls. Thirty minutes before surgery rats were pre-treated with an intraperitoneal injection of 25 mg kg−1of desmethylimipramine, an inhibitor of norepinephrine uptake. Sixteen lesioned and 16 sham-operated rats were included in the study. AVP (1 μg, i.c.v.) given 15 min before the retention testing significantly improved latencies both in lesioned and in sham-operated rats in comparison with the respective i.c.v. saline-injected animals. However, bilateral lesions to the NSL significantly diminished the facilitatory effect of AVP on recall. The insignificant decrease of spontaneous psychomotor activity in rats lesioned to the NSL was unlikely to interfere with the cognitive effect of AVP. These results suggest that dopaminergic projection to the NSL is involved in the facilitatory effect of AVP on the retrieval process in a passive avoidance situation.
The effects of a single dose of scopolamine alone and in combination with ZK 93426 (a beta-carboline antagonist at the GABAA/BZ receptor complex with weak inverse agonist activity) were tested in two ...studies. In one study (study 1) the emphasis of enquiry was on different stages of information processing measured by a psychometric battery; in the second study (study 2) performance at different stages of memory and psychomotor abilities was tested and electroencephalogram recordings and video-tracking were also performed. Each study consisted of two parts, part I in which scopolamine (0.5 mg; 1 ml) or placebo were administered subcutaneously, and part II in which scopolamine (0.5 mg; 1 ml) was administered subcutaneously followed by an intravenous injection of ZK 93426 (0.04 mg; 0.04 ml/kg) or placebo. Thirty-six volunteers, who were randomly allocated to receive one of the two treatments (n = 18 per treatment), participated in each part. In study 1 attention was measured by a continuous attention task and a rapid information processing task, vigilance was measured by a visual vigilance task, and working memory and reasoning were evaluated by a logical reasoning task. A visual memory task was also included to measure acquisition and retention. In study 2 acquisition and short term storage and retrieval were measured by a word lists-Buschke restricted reminding procedure, and retention was tested by delayed recall and recognition. Psychomotor performance was assessed by measuring tapping speed (related to gross motoric abilities) and a pegboard task (related to fine motoric abilities). A task to measure working memory, the Pauli test, was also included. In study 1 scopolamine significantly impaired performance in the attentional and vigilance tasks (P < 0.05), but there was no effect in the logical reasoning task main measurements of time and accuracy. In study 2, scopolamine also impaired performance in the psychomotor tasks (P < 0.05) and the Pauli test. ZK 93426 partially antagonised most of the effects of scopolamine on memory and attention, suggesting that an interaction between the GABA-ergic and cholinergic systems is reflected in measurements of both attention and memory. In general a dissociation was found in the effects of scopolamine on memory, i.e. scopolamine impaired performance during all acquisition measurements but left retention unaffected.
Psychomotoriktherapeutinnen und -therapeuten, die in der Schweiz zu den fest eingebundenen sonderpädagogischen Maßnahmen in der Schule gehören, sind bei bestimmten Konstellationen in ihrem ...Arbeitsumfeld verunsichert bezüglich ihrer Angebote für Schülerinnen und Schüler: Sie hinterfragen dann ihre therapeutischen Zugänge und ihre Werthaltungen, die sie grundsätzlich zwar für richtig, aber als wenig kompatibel zum Bildungssystem empfinden. Diese erlebte Einschränkung und Verunsicherung in ihrer therapeutischen Arbeit empfinden sie dann, wenn die Strukturen und Abläufe im Schulsystem aus ihrer Sicht eng und stark standardisiert sind. Der Befund stützt die These, dass eine enge Reglementierung von Berufsausübenden über administrative Vorgaben unter bestimmten Voraussetzungen langfristig zum Verschwinden der Spezifik eines Berufes und zur De-Professionalisierung führen kann. Im Forschungsprojekt "Subjektive Theorien von Psychomotoriktherapeutinnen und -therapeuten", aus welchem die Daten und Analysen stammen, waren Fragen zum Zuständigkeitskonstrukt, zum Wirksamkeitserleben und zum Umgang mit Herausforderungen zentrale Leitfragen der gering strukturierenden Leitfadeninterviews mit Therapeutinnen und Therapeuten dieses Berufes in der deutschsprachigen Schweiz. Deren Professionsverständnis bewegt sich in einem Spannungsfeld zwischen definiertem Auftrag vonseiten der Bildungsverantwortlichen einerseits und davon deutlich abweichendem, selbst konstruiertem Zuständigkeitserleben andererseits. Im Beitrag wird exemplarisch die Methodik der Rekonstruktion bei der Herausarbeitung der Befunde aus dem transkribierten Material mithilfe der integrativen, texthermeneutischen Analyse (vgl. Kruse, 2014) nachgezeichnet, Ergebnisse werden zur Diskussion gestellt und die geplanten, nächsten Schritte aufgezeigt. (Autorenreferat)
In Switzerland, psychomotor therapists are integrated into special education classrooms. However, many feel insecure regarding their effectiveness with students in certain situations. Consequently, they question their therapeutic approaches and value systems, that in principle are believed to be appropriate, but have little compatibility with the educational system. These concerns about their therapeutic work lead many psychomotor therapists to question if the structures and processes in the school system are restrictive and highly standardized. This supports the hypothesis that a close regulation of professional practitioners through administrative requirements under certain conditions can lead to the disappearance of the specific nature of a profession and de-professionalization over time. In the research project "Subjective Theories of Psychomotor Therapists", from which the data and analysis reported in this paper originated, the following themes guided the research: the competence construct, the effectiveness-experience, and dealing with challenges. Using low structured guided interviews with psychomotor therapists in German-speaking Switzerland it was possible to illustrate that their professional understanding moves in a conflict: There is a defined task from those responsible for education on the one hand, and there is a significantly deviating constructed competence experience on the other. In the article, the methodology of reconstruction in the elaboration of the findings from the transcribed material is described, using an integrative, hermeneutic analysis (Kruse, 2014). Results are presented for discussion and the steps of analysis are shown. (author's abstract)
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