[The effect of insulin on circadian rhythm of voluntary locomotor activity in rats].

Effects of single intranasal administration of 0.2 ng insulin at different moments of the projected daily cycle (ZT = 1, ZT = 7, ZT = 13 and ZT = 19) on the circadian rhythms of voluntary locomotor activity (wheel-running) were studied in Wistar male rats. Insulin administered at ZT-7 or ZT-13 induced a statistically significant phase advance by 4.4 and 5.5 hours, respectively. The administration of insulin at ZT-13 additionally induced a reduction of the period of the circadian rhythm of voluntary locomotor activity. Intranasal administration of insulin at other moments of the projected daily cycle (ZT = 1 or ZT = 19) did not induce any statistically significant change in phase or period duration of the circadian rhythms. Insulin did not cause changes in total daily activity irrespective of administration time. The results of the study suggest the role of endogenous insulin as entrainment factor for circadian oscillator in absence of the main physiological zeitgeber--cyclic afferent input from retina photoreceptors.

[Local GABA-ergic modulation of serotonergic neuron activity in the nucleus raphe magnus].

In voltage-clamp experimental on slices of the rat brainstem the effects of 5-HT and GABA on serotonergic neurons of nucleus raphe magnus were investigated. Local applications of 5-HT induced an increase in IPCSs frequency and amplitude in 45% of serotonergic cells. The effect suppressed by the blocker of fast sodium channels tetradotoxin. Antagonist of GABA receptor gabazine blocked IPSCs in neurons both sensitive and non-sensitive to 5-HT action. Applications of GABA induced a membrane current (I(GABA)), which was completely blocked by gabazine. The data suggest self-control of the activity of serotonergic neurons in nucleus raphe magnus by negative feedback loop via local GABAergic interneurons.

[Mechanisms of the respiratory activity of leptin at the level of the solitary tract nucleus].

In acute experiments on anaesthetised rats we investigated the effects of 10(-4) M leptin microinjected into the solitary tract nucleus on inspiratory-terminating Breuer-Hering reflex and ventilatory responses to hypercapnea. We found that the local administration of leptin into the area inhibited the inspiratory-terminating Breuer-Hering reflex. In contrast, ventilatory responses to hypercapnea were accentuated suggesting a modulatory effect of leptin on central chemoreceptors. The discovered physiological mechanisms are likely to play a key role for stimulating respiratory effects of leptin at the level of the solitary tract nucleus.

[Respiratory responses to microinjections of leptin into the solitary tract nucleus].

Regulatory polypeptide leptin, apart from its well-known hypothalamic effects, stimulates ventilation. The present study on anaesthetised rats was undertaken to elucidate the respiratory effects of 10(-10)-10(-4) M leptin microinjected into the solitary tract nucleus, containing a high concentration of leptin receptors. Injections of 10(-8)-10(-4) M leptin induced dose-dependent increase in ventilation, tidal volume and electric activity of inspiratory muscles; 10(-6) M leptin additionally induced a short-term increase in respiratory frequency and a shortening of both inspiratory and expiratory duration. The respiratory responses to leptin is also characterised by appearance of sighs: deep and prolonged inspirations associated with an augmented burst in the activity of the inspiratory muscles and prolonged post-sigh inter-burst interval. The results taken together with evidence of high concentration of specific leptin ObRb-receptor in the solitary tract nucleus suggest involvement of endogenous leptin in the control of breathing via dorsal structures of the respiratory center.