Júlia Szakács

The effect of obestatin on anxiety-like behaviour in mice

Obestatin is a 23 amino acid-peptide, derived from the same preproghrelin-gene as ghrelin. Obestatin was originally reported as a ghrelin antagonist with anorexigenic activity, but later it was proven to be involved in multiple processes including sleep, memory retention, anxiety, morphine-induced analgesia and withdrawal. In the present study, in male CFLP mice, by using computerised open field (OF) and elevated plus maze (EPM) tests we have investigated the behavioural effects of the acute intracerebroventricular (icv) administration of obestatin alone, and following ghrelin receptor blockage with [d-Lys3]-Growth Hormone Releasing Peptide-6 ([d-Lys3]- GHRP6) or corticotropin-releasing hormone (CRH) receptor 1 antagonism with antalarmin. Plasma corticosterone levels were measured for each treatment group by using chemofluorescent assay. Our results in the EPM test showed that obestatin reduced the percent of time spent in the open arms. The basal locomotor activity (ambulation distance and time, rearing and jumping) was not influenced significantly neither in the obestatin-treated groups, nor in those receiving pre-treatment with antalarmin or [d-Lys3]-GHRP6. The percentage of central ambulation distance however was decreased by obestatin, while the percentage of time spent in the central zone showed a decreasing tendency. The administration of antalarmin or [d-Lys3]-GHRP6 have both reversed the effect of obestatin on central ambulation. Plasma corticosterone levels were elevated by obestatin, which effect was antagonised by the injection of antalarmin. These are the first results to indicate that obestatin exerts anxiogenic-like effect in mice, which might be mediated through ghrelin receptor and CRH activation.

The effect of pituitary adenylate cyclase-activating polypeptide on elevated plus maze behavior and hypothermia induced by morphine withdrawal.

The aim of the present investigation was to study the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on morphine withdrawal-induced behavioral changes and hypothermia in male CFLP mice. Elevated plus maze (EPM) and jump tests were used to assess naloxone-precipitated morphine withdrawal-induced behavior responses. Different doses of subcutaneous (s.c.) naloxone, (0.1 and 0.2 mg/kg, respectively) were used to precipitate the emotional and psychical aspects of withdrawal on EPM and 1 mg/kg (s.c.) was used to induce the somatic withdrawal signs such as jumping, and the changes in body temperature. In our EPM studies, naloxone proved to be anxiolytic in mice treated with morphine. Chronic intracerebroventricular (i.c.v.) administration of PACAP alone had no significant effect on withdrawal-induced anxiolysis and total activity at doses of 500 ng and 1 μg. At dose of 500 ng, however, PACAP significantly counteracted the reduced motor activity in the EPM test in mice treated with morphine and diminished the hypothermia and shortened jump latency induced by naloxone in mice treated with morphine. These findings indicate that anxiolytic-like behavior may be mediated via a PACAP-involved pathway and PACAP may play an important role in chronic morphine withdrawal-induced hypothermia as well.

Kisspeptin modulates pain sensitivity of CFLP mice

HighlightsEffect of kisspeptin‐13 (KP‐13) on pain sensation was studied in male and female CFLP mice.KP‐13 reduces the pain threshold independent of the sex of mice in the tail‐flick test possibly through KISS1R activation.In addition, KP‐13 reverses morphine analgesia and reduces acute morphine tolerance.It aggravates withdrawal signs precipitated by naloxone.Furthermore, KP‐13 induces hyperthermia. ABSTRACT Kisspeptin, a hypothalamic neuropeptide, is a member of the RF‐amide family, which have been known to modify pain sensitivity in rodents. The aim of the present study was to investigate the effect of kisspeptin‐13 (KP‐13), an endogenous derivative of kisspeptin, on nociception in adult male and female CFLP mice and the possible interaction of KP‐13 with morphine on nociception. Mice were injected with different doses of KP‐13, 30, 60 and 120 min after of which the nociceptive sensitivity were assessed via the tail‐flick test. To investigate the receptor involved in the mediation a kisspeptin receptor antagonist (KP‐234) pretreatment was applied before KP‐13 administration. Furthermore, we investigated the effect of KP‐13 on the acute antinociceptive effect of morphine, on acute morphine tolerance and on naloxone‐precipitated withdrawal. Last, the Von Frey test was used in order to assess KP‐13′s effect on mechanical nociception. Our results showed that KP‐13 decreased the nociceptive threshold of both males and females independent of sex, which was prevented by KP‐234. Furthermore, KP‐13 treatment depressed the acute antinociceptive effect of morphine and attenuated the development of morphine tolerance. KP‐13 also induced a mechanical hypersensitivity. These data underlie kisspeptins hyperalgesic action and argues for the role of kisspeptin receptor 1 in the mediation of its action. Furthermore, our results suggest that central KP‐13 administration can modify the acute effects of morphine.