Viveka Hillegaart

Bio: Viveka Hillegaart is an academic researcher from Astra. The author has contributed to research in topics: Nucleus accumbens & Haloperidol. The author has an hindex of 15, co-authored 28 publications receiving 1018 citations.

High doses of oxytocin cause sedation and low doses cause an anxiolytic-like effect in male rats.

Abstract: The aim of the present investigation was to explore dose relationships for effects of oxytocin on spontaneous motor activity in the rat. Oxytocin in doses from 1-1000 micrograms/kg was given SC to male Sprague-Dawley rats, and spontaneous motor behavior was measured by means of photocell-operated open-field observations. In the rats treated with low doses of oxytocin (1-4 micrograms/kg), there was a decrease in peripheral locomotor activity. With increasing doses (250-1000 micrograms/kg), there were clear signs of sedative effects as indicated by a suppression of locomotor activity and rearing. The time course for the effect of oxytocin on peripheral activity (1 microgram/kg) and rearing (1 mg/kg) was tested. A maximal effect was obtained within 1 h and, thereafter, the behavior gradually returned to normal within 24 h. This spectrum of effects caused by oxytocin was similar to that of midazolam but different from that induced by raclopride.

Involvement of extrapyramidal motor mechanisms in the suppression of locomotor activity by antipsychotic drugs: a comparison between the effects produced by pre- and post-synaptic inhibition of dopaminergic neurotransmission.

Abstract: The effects of two proposed dopaminergic autoreceptor agonists, (−)3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) and the azepine derivative B-HT 920, on spontaneous locomotor activity, treadmill locomotion, and catalepsy in the rat have been compared with the effects produced by the postsynaptic dopamine (DA) receptor blocking agent haloperidol. It was found that the threshold dose for suppression of exploratory locomotor activity was 0.5, 0.005 and 0.2 mg/kg for (−)3-PPP, B-HT 920 and haloperidol, respectively. The corresponding doses for suppression of treadmill locomotion were 8.0, 5.12 and 0.2 mg/kg, respectively. Furthermore, (−)3-PPP and B-HT 920, in contrast to haloperidol, did not produce any catalepsy. Thus, using exploratory locomotor activity as an index of limbic forebrain DA functions and treadmill locomotion and catalepsy as indices of extrapyramidal DA functions, the DA autoreceptor agonists, in contrast to the postsynaptic antagonist, show a difference in the doses required to produce these effects. The designation of the behavioral functions as “limbic” or extrapyramidal is supported by the finding that scopolamine, 0.8 mg/kg, antagonized the haloperidol-induced suppression (0.2 mg/kg) of treadmill locomotion, but not the suppression of exploratory locomotor activity.

Effects of 8-OH-DPAT on motor activity in the rat.

Abstract: The administration of 8-OH-DPAT to rats produced a dose-dependent suppression of spontaneous locomotor activity in an open field arena. 8-OH-DPAT was administered in the dose range 12.5–1,600 μg·kg −1 SC. Vertical activity (“rearing”) was more sensitive to the treatment than horizontal activity (“locomotion”), both in terms of potency and efficacy. The activity along the walls of the open field arena (“peripheral activity”) was increased, and the rearing activity was decreased, relative to total horizontal activity and total activity, respectively. There were no effects by 8-OH-DPAT on treadmill locomotion. The rectal temperature was decreased by 8-OH-DPAT administration, not only in animals tested in the open field, but also in animals with an increased body temperature, produced by treadmill locomotion.

Effects of 5-HT and 8-OH-DPAT on forebrain monoamine synthesis after local application into the median and dorsal raphe nuclei of the rat.

Abstract: 5-HT (10 and 40 micrograms) and 8-OH-DPAT (1 and 5 micrograms) were locally applied into the dorsal or median raphe nuclei in awake, unrestrained, rats. All animals were also treated with the 5-HTP and DOPA decarboxylase inhibitor NSD-1015, 100 mg kg-1 SC, 30 min before decapitation. 5-HT or 8-OH-DPAT were administered 5 min before NSD-1015. The regional brain in vivo rate of tyrosine and tryptophan hydroxylase activity was estimated by measuring the accumulation of DOPA and 5-HTP. The following brain regions were sampled: neocortex, hippocampus, dorso-lateral neostriatum, ventro-medial neostriatum, nucleus accumbens, olfactory tubercle, globus pallidus, septum and the amygdala. Compared to normal controls, there were small and inconsistent effects on forebrain 5-HTP accumulation by saline injections into the dorsal or the median raphe (an increase in 3 out of 36 experiments), whereas strong effects by the injection procedure were noted on forebrain DOPA accumulation (an increase in 15 out of 36 experiments). Injections of 5-HT (same effect by 10 or 40 micrograms) into the dorsal raphe, produced a decrease in 5-HTP accumulation in all forebrain areas except for the hippocampus and the septum, whereas no effects were seen in any area after median raphe injections. In contrast, 8-OH-DPAT preferentially produced a decrease in forebrain 5-HTP accumulation after median raphe injections and less, but statistically significant effects by dorsal raphe injections. The 8-OH-DPAT injection into the median raphe primarily affected limbic forebrain areas (hippocampus, nucleus accumbens, ventro-medial neostriatum, amygdala and the septum). This dissociation of the effects of 5-HT and 8-OH-DPAT on forebrain 5-HT synthesis after local application into the dorsal or the median raphe strongly supports the contention of heterogeniety in the brain 5-HT receptor population in terms of receptor subtypes and/or receptor regulation.

The Oxytocin Receptor System: Structure, Function, and Regulation

Abstract: The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation. Such stimuli also lead to an intranuclear release of OT. Moreover, oxytocinergic neurons display widespread projections throughout the central nervous system. However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart. The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via Gq proteins to phospholipase C-β. The high-affinity receptor state requires both Mg2+ and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has bee...