Biomedical subjects

J Adrien

Publications and source records attributed to J Adrien.

At least 37 records · Page 2Linked to original sources

PubMed1995

Induction of rapid eye movement sleep by carbachol infusion into the pontine reticular formation in the rat.

Cholinergic regulation of sleep and wakefulness was studied in freely moving rats locally infused with various doses of carbachol into the pontine reticular formation. Induction of REM sleep occurred when carbachol was infused specifically into the posterior oral pontine reticular nucleus (PnO). This effect was observed with 1-10 ng of carbachol, and lasted for at least 6 h. It was antagonized by atropine (100-200 ng) infused into the same site 15 min before carbachol (10 ng), indicating that REM sleep induction resulted from the stimulation of pontine muscarinic receptors. High doses of carbachol (500 ng) did not affect REM sleep but enhanced wakefulness. Cholinergic mechanisms within the PnO may play a critical role in the regulation of REM sleep in the rat.

Animals↗

PubMed1995

In situ hybridization evidence for the synthesis of 5-HT1B receptor in serotoninergic neurons of anterior raphe nuclei in the rat brain.

The regional distribution of the mRNA encoding the serotonin 5-HT1B receptor was studied in the central nervous system of the rat by in situ hybridization histochemistry and Northern blot analysis. A 180 base pair probe, corresponding to a highly selective portion of the third intracellular loop of the rat 5-HT1B receptor, was used. In most regions, a single 5 kb message was found by Northern blot analysis. However, two additional bands (2.5 and 4 kb) were detected in the striatum. The rank order of 5-HT1B mRNA abundance was striatum >> septum = ventral tegmentum > or = colliculi = hypothalamus = hippocampus > brain stem > or = cerebellum > or = dorsal horn of the spinal cord > cerebral cortex > or = ventral horn of the spinal cord > olfactory tubercle. This distribution was confirmed by in situ hybridization, which further revealed that the 5-HT1B mRNA was present in dorsal root ganglia, the layer IV of the cerebral cortex, the Purkinje cell layer of the cerebellum, the pyramidal neurons in the CA1 area of the hippocampus, and the dorsal and median raphe nuclei. In situ hybridization was also performed in nomifensine (10 mg/kg/i.p.)-pretreated rats whose serotoninergic neurons were extensively and selectively lesioned by microinjection of 5,7-dihydroxytryptamine (8 micrograms/1 microliter) directly into the anteroventral vicinity of anterior raphe nuclei 3 weeks before sacrifice. In lesioned rats, 5-HT1B mRNA was present in the same areas and at the same levels as in control rats, except in the dorsal and median raphe nuclei, where a marked decrease (-75%) in its local concentration was observed. These data provide the first demonstration of the synthesis of 5-HT1B receptor within serotoninergic neurons, as expected of their presynaptic autoreceptor function at the level of serotoninergic terminals.

5,7-Dihydroxytryptamine↗

PubMed1995

Are postsynaptic 5-HT1A receptors involved in the anxiolytic effects of 5-HT1A receptor agonists and in their inhibitory effects on the firing of serotonergic neurons in the rat?

Previous studies have shown that injection of 5-hydroxytryptamine (serotonin) receptor agonists in the dorsal raphe nucleus (DRN) to stimulate somatodendritic 5-HT1A autoreceptors or in the hippocampus to stimulate postsynaptic 5-HT1A receptors, induces anxiolytic-like effects in the rat. The mechanisms triggered by the latter treatment were investigated by measuring both the electrical activity of serotonergic DRN neurons and the anxiolytic response in rats receiving injections with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) or ipsapirone into the dorsal hippocampus. Anxiety-related behavior was estimated by recording the time of ultrasonic vocalization (USV) due to electric foot shocks under standardized conditions. Intrahippocampal application of 8-OH-DPAT or ipsapirone produced a dose-dependent inhibition of the firing of serotonergic DRN neurons and of the shock-induced USV response. However, the range of efficient doses of 8-OH-DPAT via the intrahippocampal route (1-10 micrograms/rat) was larger than that using the i.v. route of injection (0.15-2.5 micrograms/rat). Furthermore, maximal inhibition of the firing of DRN serotonergic neurons occurred earlier when 8-OH-DPAT was injected i.v. (within 1-2 min) than when it was injected into the dorsal hippocampus (within 5 min). Interestingly, the injection of 8-OH-DPAT into the striatum, where 5-HT1A receptors are hardly detectable, or a lateral ventricle, also yielded dose-dependent reduction in both the firing rate of serotonergic DRN neurons and the USV response. Finally, local lesion with ibotenic acid to eliminate postsynaptic 5-HT1A receptors did not alter the inhibitory effects of intrahippocampal application of 8-OH-DPAT on the firing of serotonergic DRN neurons and the USV response. These data indicated that postsynaptic 5-HT1A receptors were not responsible for the inhibitory effects of 8-OH-DPAT and ipsapirone injected in forebrain areas on the electrical activity of serotonergic neurons and the USV response in rats. As shown by the autoradiographic labeling by [3H]8-OH-DPAT at distance from its injection site in the dorsal hippocampus, the diffusion of 5-HT1A receptor agonists (from injected areas in the forebrain to the DRN where they directly inhibit the electrical activity of serotonergic neurons) more likely accounted for their anxiolytic-like effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1994

Effects of acute and chronic treatment with amoxapine and cericlamine on the sleep-wakefulness cycle in the rat.

Antidepressant drugs, such as the tricyclics and the serotonin reuptake inhibitors, are well known to decrease paradoxical sleep and occasionally increase slow wave sleep in human and in animals. In order to examine whether amoxapine (a mixed NA reuptake blocker and 5-HT2/5-HT3 antagonist) and cericlamine (a selective 5-HT reuptake inhibitor) exert the same effect in rats, and to investigate the possible relationships between sleep, the action of antidepressants and the serotoninergic system, the effects of these two different drugs were examined under acute and chronic conditions. Acutely, amoxapine (1, 5 and 10 mg/kg; i.p.) and cericlamine (1, 8, 16 and 32 mg/kg; i.p.) decreased paradoxical sleep and increased deep slow wave sleep especially when they were given at a low dose. When administered for 14 days, amoxapine induced a sustained decrease of paradoxical sleep during the whole treatment, while some tolerance was observed with regard to the inhibitory effect of cericlamine on this state of sleep. In addition, a rebound of paradoxical sleep occurred on the first day of cericlamine withdrawal. Thus, amoxapine and cericlamine exerted the same effects on the states of vigilance in the rat as do other antidepressants. The effects of cericlamine on sleep probably reflect its blocking action on 5-HT uptake, whereas the more complex effects of amoxapine might involve its 5-HT2/5-HT3 antagonist properties.

Amoxapine↗

PubMed1994

Central pre- and postsynaptic 5-HT1A receptors in rats treated chronically with a novel antidepressant, cericlamine.

Biochemical and electrophysiological approaches were used to assess the possible changes in 5-hydroxytryptamine (serotonin) 5-HT1A receptors in the rat brain after a long-term treatment with cericlamine [2-(3,4-dichlorobenzyl)-2-dimethylamino-1-propanol], a novel serotonin reuptake inhibitor with antidepressant properties. Possible changes in other serotonin receptor binding sites (5-HT2A, 5-HT2C and 5-HT3) were also investigated after this treatment. Cericlamine was injected for 2 weeks at a dose (16 mg/kg i.p., twice daily) that ensured complete prevention of 4-methyl-alpha-ethyl-meta-tyramine-induced depletion of brain serotonin. In vitro binding and quantitative autoradiographic studies showed that neither 5-HT1A, 5-HT2A, 5-HT2C nor 5-HT3 receptor binding sites in various brain areas were affected by the 14-day treatment with cericlamine. Although forskolin-stimulated adenylate cyclase activity was significantly increased in hippocampal homogenates from cericlamine-treated rats, the reduction in this enzymatic activity due to 5-HT1A receptor stimulation by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was unchanged in these animals as compared with controls. In contrast, in vitro and in vivo electrophysiological recordings of serotoninergic neurons in the dorsal raphe nucleus revealed a clearcut functional desensitization of somatodendritic 5-HT1A autoreceptors. Thus the potency of 8-OH-DPAT and ipsapirone to depress the firing rate of these neurons in brain stem slices was significantly reduced after the 2-week treatment with cericlamine. In vivo, the potency of an injection of cericlamine to inhibit the discharge of serotoninergic neurons was also markedly less in rats that had been pretreated for 2 weeks with this drug as compared with controls. However, the inhibitory effects of systemically injected 8-OH-DPAT and ipsapirone on the electrical activity of serotoninergic neurons were as pronounced in cericlamine-treated rats as in controls. In addition, the reduction in serotonin synthesis due to an acute treatment with 8-OH-DPAT (0.1 or 0.3 mg/kg s.c.) was not significantly different in both groups of rats. These data support the idea that postsynaptic (in the hippocampus) and somatodendritic (in the dorsal raphe nucleus) 5-HT1A receptors are differently regulated in the rat brain, because only the latter receptors desensitized after a long-term blockade of serotonin reuptake by cericlamine. They also suggest that the inhibitory influence of systemically administered direct 5-HT1A agonists such as 8-OH-DPAT and ipsapirone on the electrical and metabolic activity of serotoninergic neurons does not result solely from the stimulation of somatodendritic 5-HT1A autoreceptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1993

(-)Tertatolol is a potent antagonist at pre- and postsynaptic serotonin 5-HT1A receptors in the rat brain.

The potential 5-HT1A antagonist properties of the beta-antagonist tertatolol were assessed using biochemical and electrophysiological assays in the rat. (+/-) Tertatolol bound with high affinity (Ki = 38 nM) to 5-HT1A sites labelled by [3H]8-OH-DPAT in hippocampal membranes. The (-)stereoisomer (Ki = 18 nM) was about 50-fold more potent than the (+)stereoisomer (Ki = 864 nM) to inhibit the specific binding of [3H]-8-OH-DPAT. As expected of a 5-HT1A antagonist, (-)tertatolol prevented in a concentration-dependent manner (Ki = 24 nM) the inhibitory effect of 8-OH-DPAT on forskolin-stimulated adenylate cyclase activity in rat hippocampal homogenates. Furthermore in vivo pretreatment with (-)tertatolol (5 mg/kg s.c.) significantly reduced the inhibitory influence of 8-OH-DPAT (0.3 mg/kg s.c.) on the accumulation of 5-hydroxytryptophan in various brain areas after the blockade of aromatic L-amino acid decarboxylase by NSD-1015 (100 mg/kg i.p.). In vitro (in brainstem slices; Ki approximately 50 nM) and in vivo (in chloral hydrate anaesthetized rats; ID50 approximately 0.40 mg/kg i.v.), (-)tertatolol prevented the inhibitory effects of the 5-HT1A receptor agonists 8-OH-DPAT, ipsapirone and lesopitron on the firing rate of serotoninergic neurones within the dorsal raphe nucleus. In about 25% of these neurones, the basal firing rate was significantly increased by (-)tertatolol (up to +47% in vitro, and +30% in vivo). These data indicate that (-)tertatolol is a potent competitive antagonist at both pre (in the dorsal raphe nucleus)-and post (in the hippocampus)-synaptic 5-HT1A receptors in the rat brain.

5-Hydroxytryptophan↗

PubMed1993

Effects of ipsapirone, a 5-HT1A agonist, on sleep/wakefulness cycles: probable post-synaptic action.

The effects of ipsapirone, a ligand of the 5-HT1A receptors and a new potential anxiolytic, on sleep/wakefulness regulation were examined in the rat. Injected i.p. at 1, 3 and 5 mg kg-1, this compound induced a dose-dependent reduction of paradoxical sleep for 2 to 4 hours, followed, at a dose of 5 mg kg-1, by a secondary rebound. The other states of vigilance were not modified, except at the latter dose where the amounts of wakefulness were enhanced initially and decreased secondarily, while those of SWS were enhanced from 2 to 4 hours post-treatment. The effects of ipsapirone (3 mg kg-1) persisted after infusion of the neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe nucleus which induced the sub-total destruction of the serotoninergic system. Thus, the action of the 5-HT1A agonist ipsapirone on sleep/wakefulness cycles probably involves the stimulation of the post-synaptic 5-HT1A receptors.

Journal Article↗

PubMed1992

Central action of 5-HT3 receptor ligands in the regulation of sleep-wakefulness and raphe neuronal activity in the rat.

Anxiolytic drugs, such as the benzodiazepines and the azapirones (ipsapirone, gepirone, buspirone), are well known to affect states of vigilance and to decrease the firing rate of serotoninergic neurones within the dorsal raphe nucleus in rats. In order to examine whether the newly developed 5-HT3 antagonists with potential anxiolytic properties act through similar mechanisms, the effects of several of such antagonists: MDL 72222, ICS 205-930, ondansetron and/or zacopride on both sleep-wakefulness and the discharge of serotoninergic neurones within the dorsal raphe nucleus were investigated in rats. When tested in a wide range of doses (0.05-10 mg/kg, i.p.), none of these drugs significantly affected the states of vigilance, except ondansetron, at 0.1 mg/kg, which increased paradoxical sleep for the first 2 hr after administration and MDL 72222, at 10 mg/kg, which reduced both paradoxical and slow wave sleep and increased wakefulness for the same initial period after treatment. In vivo, in chloral hydrate anaesthetized rats, as well as in vitro, in slices of brain stem, none of the 5-HT3 antagonists tested affected the firing rate of serotoninergic neurones. Similarly, no change in the electrical activity of serotoninergic neurones could be evoked in vitro by superfusion of the tissue with the 5-HT3 agonists, phenylbiguanide (10 microM) and 2-methyl-5-HT (1 microM). At a larger concentration (10 microM), the latter compound reduced the neuronal discharge probably through the stimulation of somatodendritic 5-HT1A autoreceptors since this effect, as that of ipsapirone, could be prevented by 10 microM l-propranolol. Comparison of these data with those obtained with benzodiazepines and 5-HT1A agonists of the azapirone series, supports the concept that different mechanisms are responsible for the anxiolytic-like properties of 5-HT3 agonists, compared to those of other anxiolytic drugs.

Animals↗

PubMed1992

Effect of the selective lesion of serotoninergic neurons on the regional distribution of 5-HT1A receptor mRNA in the rat brain.

The effects of the selective lesion of serotoninergic neurons by an intra-raphe administration of 5,7-dihydroxytryptamine on the 5-HT1A receptor protein and the 5-HT1A receptor mRNA were examined in various regions of the rat brain using specific antibodies and an antisense riboprobe, respectively. Twenty one days after the treatment, the 5-HT1A receptor protein was no longer detected within the dorsal raphe nucleus but was still present in the hippocampus and entorhinal cortex. Quantitative in situ hybridization showed an 85% decrease in the levels of 5-HT1A receptor mRNA within the dorsal raphe nucleus, but no significant change in the hippocampus, interpeduncular nucleus and entorhinal cortex of 5,7-dihydroxytryptamine-treated rats. These data demonstrate that 5-HT1A receptors are synthesized by serotoninergic neurons in the dorsal raphe nucleus, and by neurons located postsynaptically with regard to serotoninergic projections in other areas. The unchanged levels of 5-HT1A receptor mRNA in the hippocampus, interpeduncular nucleus and entorhinal cortex three weeks after the extensive lesion of serotoninergic neurons are consistent with the absence of 5-HT1A receptor up regulation already reported under this condition.

5,7-Dihydroxytryptamine↗

PubMed1991

Antidepressant-like effects of buspirone mediated by the 5-HT1A post-synaptic receptors in the learned helplessness paradigm.

The 5-HT1A receptor agonists buspirone and 8-OH-DPAT have strong effects on serotoninergic systems. Mediated by both pre- and post-synaptic 5-HT1A receptors, these pharmacological effects might predict both antidepressant and antianxiety activities. In animal models sensitive to antidepressant drugs, the 5-HT1A agonists administered i.p. have been shown to mimic the behavioral effects of tricyclics. In the present study, the learned helplessness paradigm was used to assess the possible role of pre- or post-synaptic 5-HTIA receptors in this effect. The ability of buspirone compared with 8-OH-DPAT to reduce helpless behavior was investigated after local microinjections (0.1 or 1.0 micrograms in 0.5 microliters) into the raphe nuclei or into the septum. The results indicate that microinjections of buspirone or 8-OH-DPAT into the raphe nuclei did not reverse helpless behavior; in contrast, microinjections of both 5-HTIA agonists into the septum reverse helpless behavior. These results suggest that antidepressant-like properties of buspirone and 8-OH-DPAT may be mediated, in this test, by the post-synaptic 5-HTIA receptors through functional enhancement of the 5-HT transmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1991

Regulation of noradrenergic coerulean neuronal firing mediated by 5-HT2 receptors: involvement of the prepositus hypoglossal nucleus.

Previous studies have indicated a 5-HT2-mediated inhibitory influence on unit activity in the locus coeruleus. In the present work, attempts were made to determine which area(s) of the brain is (are) involved in this effect: (1) Microiontophoretic application of serotoninergic compounds (quipazine, ketanserin, RU 24969 (Roussel Uclaf), 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT), metergoline, serotonin) in the locus coeruleus, did not alter the coerulean discharge. Local microinjection of quipazine or ketanserin in the area of the locus coeruleus, as well as in one of its major afferents, the prepositus hypoglossi, had no effect on the unit activity in the locus coeruleus. (2) Section of the forebrain, caudal to the frontal cortex (rich in 5-HT2 receptors), did not modify the effects of coerulean activity of quipazine-ketanserin injected systemically: quipazine induced an inhibition which was reversed by ketanserin. In contrast, these effects were significantly reduced after the bilateral or contralateral lesion of the prepositus hypoglossi. It is concluded that the prepositus hypoglossal nucleus is part of the network responsible for the 5-HT2-mediated control of unit activity in the locus coeruleus.

Animals↗

PubMed1991

Sleep-wakefulness patterns in the helpless rat.

Sleep-wakefulness patterns were analyzed during a 15-day period in the rat, in relation to induction of helplessness. After a session of inescapable electric footshocks, rats did exhibit escape deficits in avoidance conditioning as classically described, and their spontaneous sleep-wakefulness patterns were not different from those of controls. However, reduced PS latency and increased PS amounts were observed in the helpless group after shuttle-box sessions, especially during the initial period after the induction of helplessness. Such modifications of PS latency and PS amounts are evocative of the sleep impairments classically observed in endogenous depression.

Animals↗

PubMed1989

Lesion of the PGO pathways in the kitten. II. Impairment of physiological and morphological maturation of the lateral geniculate nucleus.

Suppression of the geniculate ponto-geniculo-occipital (PGO) waves by bilateral lesions of PGO pathways at the mesencephalic level in 15-day-old kittens has been shown to induce a significant reduction of the mean discharge frequency recorded in the lateral geniculate nucleus (LGN) during paradoxical sleep. The present paper reports that one month after the bilateral lesion (i.e., 6-7 weeks of age) important deficits in the maturation of the LGN were observed: (1) electrophysiologically, the latencies of the LGN cellular responses to stimulation of the optic chiasm were significantly longer than those of age-paired controls or of unilaterally lesioned animals, and the proportion of visual cells characterized as type X by stimulation of the visual field was smaller; and (2) morphologically, the volume of the LGN and the size of its neuronal somata were smaller than those in control. These data suggest that bilateral suppression of extraretinal PGO afferents to the LGN in the kitten induces a significant delay in the development of this nucleus.

Action Potentials↗

PubMed1989

Vasotocin increases quiet sleep and suppresses active sleep in newborn cats. Opposite effects after vasotocin immunoneutralization.

One picogram of synthetic arginine vasotocin (AVT) administered into the lateral ventricle of newborn cats aged 7-9 days, increased the amount of quiet sleep and markedly decreased the amount of active sleep. Ten pg AVT completely suppressed active sleep during the recording time of 3 hr. The increase in the quiet sleep occurred within 5-7 min and lasted for the entire recording time of 3 hr. An undiluted specific AVT antiserum (10 microliters) administered into the lateral ventricle, induced opposite effects suppressing quiet sleep and increasing active sleep. It is concluded that in newborn cats both AVT and the AVT antiserum induce the same hypnogenic effects as in the adult cats.

Animals↗

PubMed1989

Biochemical and electrophysiological evidence for an agonist action of CM 57493 at pre- and postsynaptic 5-hydroxytryptamine1A receptors in brain.

The potential interaction of CM 57493 [4-(3-trifluoromethyl-phenyl)-1-(2-cyanoethyl)-1,2,3,6-tetrahydropyri din e] with central 5-hydroxytryptamine (5-HT) receptors was assessed using biochemical and electrophysiological tests in the rat and in the cat. In vitro binding assays with rat brain membranes revealed that CM 57493 bound to 5-HT1A sites in a concentration range (pIC50 = 7.1) at least two orders of magnitude lower than that required for its interaction with 5-HT1B/5-HT1D, 5-HT2, 5-HT3 and 5-HTPre sites. The affinity of CM 57493 for 5-HT1A sites labeled by [3H]-8-OH-DPAT in hippocampal membranes was enhanced by Mn++ and reduced by GTP, as expected for an agonist. Like 8-OH-DPAT, CM 57493 inhibited forskolin-activated adenylate cyclase activity in hippocampal homogenates. The inhibitory effects of these two compounds were not additive and were prevented by 5-HT1A antagonists such as spiperone and dl-propranolol. In vivo treatment with CM 57493 decreased the levels of 5-hydroxyindole acetic acid in various brain areas, as observed with other 5-HT1A agonists such as 8-OH-DPAT and ipsapirone. Electrophysiological recording within the dorsal raphe nucleus in chloral hydrate anesthetized rats showed that CM 57493 administration induced a dose-dependent reduction of the spontaneous firing of serotoninergic neurons. In vitro, CM 57493 (5-20 microM) also reduced neuronal firing in the nucleus raphe dorsalis within brainstem slice, and this effect could be prevented by dl-propranolol. Finally, in cats pretreated with reserpine, CM 57493 induced a decrease in ponto-geniculo-occipital activity, which could be antagonized by methiothepin.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1988

Serotonergic regulation of noradrenergic coerulean neurons: electrophysiological evidence for the involvement of 5-HT2 receptors.

To determine the type of serotonergic receptor involved in the modulation of noradrenergic neuronal activity in the locus coeruleus, the effects of 4 systemically administered serotonergic drugs were tested on the firing rate of noradrenergic neurons in the locus coeruleus of rats under chloral hydrate anaesthesia. The serotonergic agonist, quipazine (1 mg/kg), and the selective 5-HT2 agonist, DOB (50-100 micrograms/kg), induced a pronounced decrease of the discharge frequency. This effect could be prevented or reversed by the selective 5-HT2 antagonist, ketanserin (4-8 mg/kg). Ketanserin alone and the 5-HT1 agonist, RU 24969, had no or a weak excitatory action on the neuronal activity of the locus coeruleus. We conclude that the serotonergic control of noradrenergic neurons in the locus coeruleus is mediated by post-synaptic 5-HT2 receptors because the quipazine-ketanserin effects on this unit activity persisted after depletion of serotonergic presynaptic stores.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1988

Adaptive changes of beta-adrenergic receptors after neonatal locus coeruleus lesion: regulation of serotoninergic unit activity.

Spontaneous activity of 5-hydroxytryptamine (5-HT) neurons in the dorsal raphe nucleus (DRN) was recorded in adult rats that had undergone a bilateral locus coeruleus (LC) lesion during the neonatal period. The susceptibility of this neuronal firing to beta-adrenergic manipulation was tested. Microiontophoretic application of the beta-blockers d,l-propranolol and acebutolol inhibited the firing of DRN cells in lesioned rats but not in control animals. This effect was specific to beta-receptors since the effects of pharmacological manipulation of other receptors--5-HT, gamma-aminobutyric acid (GABA), alpha-adrenoceptors--were identical in lesioned and control animals. The present data demonstrate that a neonatal noradrenergic lesion allowed the persistence of a beta-regulation of DRN neuronal firing, which in young rats is normally only transient.

Acebutolol↗

PubMed1988

Age-dependent beta-adrenergic response of neuronal discharge in the raphe dorsalis: evidence of a transient regulation.

Extracellular recordings from raphe dorsalis neurons in rats during development were performed, and the response to iontophoretically applied beta-antagonists was analysed. In pups younger than 2 weeks, raphe dorsalis firing was totally or partially inhibited by application of beta-antagonists, while after 2 weeks of age the neurons were insensitive to the same application. The beta-receptors appeared to be involved in the control of raphe firing during a transient period of ontogenesis and thus the disappearance of beta-regulation at older ages may reflect the regression of this population of neurotransmitter receptors.

Adrenergic beta-Antagonists↗