Cardioinhibitory actions of clonidine assessed by cardiac vagal motoneuron recordings.

BACKGROUND: Cardiac vagal activity is now considered as an important therapeutic target. However, there is a lack of direct data on how cardiac vagal motoneurons respond to parasympathomimetic agents. METHODS: Rats were anesthetized with urethane and mechanically ventilated. Single-unit activity was recorded in the nucleus ambiguus from cardiac vagal motoneurons, identified by antidromic activation from the cardiac vagal branch and their barosensitivity. RESULTS: Nitroprusside lowered systolic blood pressure, increased heart rate and inhibited cardiac vagal motoneuron activity (n = 5 cells in five rats). Clonidine 1-100 microg kg(-1) intravenously, however, lowered systolic blood pressure, but it increased cardiac vagal motoneuron activity (n = 8 cells in eight rats). It also enhanced their barosensitivity. An unsuspected further finding was that clonidine significantly increased the occurrence of cardiac vagal motoneuron firing spikes separated by short (< 30 ms) interspike intervals ('doublet'). CONCLUSION: Such grouped patterns are known to enhance neurotransmitter release. Therefore, these data provide a new mechanism by which clonidine can further potentiate parasympathetic actions on the heart.

Effect of catecholamine depletion on increased blood pressure lability upon emergence from halothane anesthesia in rats: the role of sympathetic nervous activity in postanesthetic circulatory instability.

PURPOSE: Circulatory instability is often observed upon emergence from general anesthesia. The increased blood pressure (BP) lability has been associated with poor clinical outcome. However, its underlying mechanisms are not fully understood. Thus, we investigated a possible role of the sympathetic nervous system (SNS) and cardiac baroreflex in the increased pressure lability observed upon emergence from general anesthesia. METHODS: Male rats (n = 16) were allocated to two groups, i.e., (1) a control group (n = 8) and (2) an alpha-methylparatyrosine (alpha-MPT; an inhibitor of tyrosine hydroxylase)-treated group (n = 8). In the alpha-MPT-treated group, in order to deplete catecholamines both in the central nervous system and in the SNS, alpha-MPT (300 mg x kg(-1)) was injected intraperitoneally (i.p.), administered twice, 4 and 2 h before halothane discontinuation (total dose, 600 mg x kg(-1) i.p.). In the control group, saline was administered at identical time-points. Systolic BP (SBP) lability was evaluated on a beat-by-beat basis, using the coefficient of variation of SBP, and the occurrence of slow and rapid rises in SBP and their amplitude, while the cardiac baroreflex slope was calculated using the "sequences" method. RESULTS: In the control group, heart rate, SBP, and the three indices of BP lability (i.e., the 3 indices of BP lability are: coefficient of variation of SBP, number of slow and rapid rises in pressure, amplitude of slow and rapid rises in pressure) all increased upon emergence from anesthesia (P < 0.05). Such increases were all blunted in the alpha-MPT-treated group, with the increases in the three indices of BP lability almost entirely suppressed (P < 0.05). The cardiac baroreflex slope was similarly decreased in both groups (P < 0.05). CONCLUSION: The postanesthetic increase in pressure lability seems largely a consequence of increased sympathetic activity, irrespective of any change in cardiac baroreflex sensitivity.

In vivo comparison of two 5-HT1A receptors agonists alnespirone (S-20499) and buspirone on locus coeruleus neuronal activity.

The aim of the present study was to compare, in chloral-hydrate anaesthetized rats, the alpha(2)-adrenergic properties of the selective 5-HT(1A) receptor agonist, alnespirone (S-20499), with those of buspirone, a 5-HT(1A) receptor agonist exhibiting potent alpha(2)-adrenoceptor antagonist properties via its principal metabolite, 1-(2-pyrimidinyl)-piperazine. Both locus coeruleus spontaneous firing activity and noradrenaline release in the medial prefrontal cortex were potently inhibited by the alpha(2)-adrenoceptor agonist clonidine, at a dose of 40 microg/kg (i.p.). Such an inhibition was neither prevented nor reversed by alnespirone (10 mg/kg, i.p.), while buspirone, at the same dose, potently antagonized the locus coeruleus inhibitory effects of clonidine. These data demonstrate that, in contrast with some aryl-piperazine compounds (such as buspirone), alnespirone, either on its own or via a possible metabolite such as buspirone, is devoid in vivo of significant alpha(2)-adrenoceptor antagonist properties.

The switch of subthalamic neurons from an irregular to a bursting pattern does not solely depend on their GABAergic inputs in the anesthetic-free rat.

The subthalamic nucleus (STN) powerfully controls basal ganglia outputs and has been implicated in movement disorders observed in Parkinson's disease because of its pathological mixed burst firing mode and hyperactivity. A recent study suggested that reciprocally connected glutamatergic STN and GABAergic globus pallidus (GP) neurons act in vitro as a generator of bursting activity in basal ganglia. In vivo, we reported that GP neurons increased their firing rate in wakefulness (W) compared with slow-wave sleep (SWS) without any change in their random pattern. In contrast, STN neurons exhibited similar firing rates in W and SWS, with an irregular pattern in W and a bursty one in SWS. Thus, the pallidal GABAergic tone might control the STN pattern. This hypothesis was tested by mimicking such variations with microiontophoresis of GABA receptor ligands. GABA agonists specifically decreased the STN firing rate but did not affect its firing pattern. GABA(A) (but not GABA(B)) antagonists strongly enhanced the STN mean discharge rate during all vigilance states up to three to five times its basal activity. However, such applications did not change the typical W random pattern. When applied during SWS, GABA(A) antagonists strongly reinforced the spontaneous bursty pattern into a particularly marked one with instantaneous frequencies reaching 500-600 Hz. SWS-W transitions occurring during ongoing antagonist iontophoresis invariably disrupted the bursty pattern into a random one. Thus GABA(A) receptors play a critical, but not exclusive, role in regulating the excitatory STN influence on basal ganglia outputs.