Neuroscience
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[3H]Noradrenaline release was studied in cultured sympathetic neurons derived from superior cervical ganglia of neonatal rats. Acetylcholine elicited a concentration- and time-dependent increase in 3H outflow which was half-maximal at about 300 microM and within 5 s. The overflow induced by 10 s exposure to 300 micro A acetylcholine was reduced by the nicotinic antagonist hexamethonium, but increased by the muscarinic antagonist atropine. ⋯ The acetylcholine-induced transmitter release is based on two mechanisms, one involving and the other one bypassing voltage-dependent Ca2+ channels. alpha2-Adrenoceptor activation reduces voltage-activated Ca2+ currents and effects exclusively the component of acetylcholine-induced release which involves voltage-dependent Ca2+ channels. These results support the hypothesis that voltage-activated Ca2+ channels are the sole site of autoinhibitory alpha2-adrenergic effects on transmitter release from rat sympathetic neurons. The inhibitory effects of alpha2-adrenoceptor agonists and antagonists on currents through nicotinic acetylcholine receptors are not mediated by an alpha2-adrenoceptor.
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Previous electrophysiological studies have shown that spontaneously active mesencephalic 5-hydroxytryptaminergic neurons of anaesthetized or freely moving animals fire solitary spikes in a slow, regular pattern. In the present study, using extracellular single unit recordings from dorsal and median raphe neurons of the anaesthetized rat, an additional electrophysiological property of a sub-population of presumed 5-hydroxytryptaminergic neurons was observed. These neurons, during their otherwise regular firing pattern, repeatedly fired two (or occasionally three or even four) spikes where only one was expected. ⋯ Repetitive firing neurons occurred in both the dorsal and median raphe nuclei, although they were much more frequent in the dorsal raphe nucleus (91 of 332 neurons). The occurrence of repetitive firing neurons in the midbrain raphe nuclei is a newly described phenomenon which may indicate unique properties of a sub-population of 5-hydroxytryptaminergic neurons. In functional terms, it could modify both axonal and dendritic 5-hydroxytryptamine release, and provide an additional option for neuronal information signalling.
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The effect intracerebroventricular injections of angiotensin II (0.1 nm), angiotensin-(1-7) (1 or 100 nm) and carbachol (500 ng) on c-fos expression was examined in the forebrain of Lister hooded rats. Intense staining of the c-Fos protein was found in the median preoptic nucleus, organum vasculosum of the lamina terminalis, subfornical organ, paraventricular nucleus and supraoptic nucleus after angiotensin II and carbachol Angiotensin II caused significantly more c-fos expression in the ventral median preoptic nucleus and organum vasculosum of the lamina terminalis than carbachol, whereas in the paraventricular and supraoptic nuclei this was reversed, with carbachol having a greater effect on c-fos expression in these areas. Angiotensin-(1-7), however, only induced c-Fos protein in the organum vasculosum of the lamina terminalis and median preoptic nucleus with the number and the intensity of staining of the nuclei significantly less in both areas than after angiotensin II or carbachol. ⋯ Angiotensin II and carbachol caused an approximate five-fold increase in plasma vasopressin levels compared to cerebrospinal fluid-injected rats, but angiotensin-(1-7) had no effect on vasopressin release. Therefore, three compounds with widely differing effects on thirst, sodium appetite and vasopressin release induce distinctive patterns of c-fos protein expression in the forebrain. By combining experimental approaches in this way it is possible to determine areas of the brain which are involved in certain behavioural and endocrine responses.
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While B2 receptors mediate pain and hyperalgesia induced by bradykinin, in normal rats, recent reports indicate that, in the setting of inflammation, B1 receptors also mediate pain and hyperalgesia. Since bradykinin-induced hyperalgesia in normal rats is mediated by prostaglandins released from the postganglionic sympathetic neurons, we have evaluated the contribution of the sympathetic nervous system to the hyperalgesia induced by bradykinin, a preferential B2-receptor agonist, and des-Arg9-bradykinin, a major metabolite of bradykinin and a selective B1-receptor agonist. Mechanical hyperalgesia was quantified by the Randall-Selitto paw-withdrawal method. ⋯ These results are consistent with the suggestions that B2 receptors mediate bradykinin-induced cutaneous hyperalgesia in the normal rat hindpaw. The hyperalgesia induced by bradykinin, 48 h post injection of complete Freund's adjuvant is mediated by both B1 and B2 receptors, that by des-Arg9-bradykinin is mediated by B1 receptors. The hyperalgesia induced by both agents is dependent on the presence of intact sympathetic postganglionic neurons.
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Both acute central administration of exogenous, and stress-induced release of endogenous corticotropin-releasing factor result in electrophysiological activation of the noradrenergic neurons constituting the locus coeruleus. The present experiments were designed to examine whether single (1) or repeated (8) intracerebroventricular pretreatment with exogenous corticotropin-releasing factor would alter locus coeruleus electrophysiological responsivity to subsequent corticotropin-releasing factor challenge in rats. A single corticotropin-releasing factor (3 microg) pretreatment significantly attenuated challenge-induced locus coeruleus activation 24 and 72, but no 96 h later, while a single vehicle pretreatment had no significant effect on the response to subsequent challenge at any pretreatment-to-test interval. ⋯ Additionally, in rats repeatedly pretreated with vehicle, carbachol challenge induced an increase in locus coeruleus activity equal to that induced in naive controls. These results indicate that prior exposure to corticotropin-releasing factor, or the repeated mild stress of vehicle infusions, reduces locus coeruleus responsiveness to corticotropin-releasing factor, and reveal that the relationship between these two neurotransmitter systems is modifiable. This altered relationship may contribute to stress-related affective disorders in which both systems have been implicated.