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PubMed1997

Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms.

A series of ten experiments examined the effects of profound central 5-HT depletion on attentional performance in the rat in the five-choice serial reaction time task, and also determined the effects of such depletion on responding affected by d-amphetamine and by selective dopamine receptor antagonists. Rats were trained to detect and locate brief visual stimuli randomly presented in one of five spatial locations. When performance had stabilised (> 80% correct, < 20% omissions), selective central 5-HT depletion was induced by intracerebroventricular administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) following pretreatment with both a noradrenergic and a dopaminergic re-uptake inhibitor. The lesioned animals performed the five-choice serial reaction time task with the same degree of accuracy as the sham-operated controls. However, 5-HT depletion reduced the percentage of omitted trials and increased the number of premature/anticipatory responses. This pattern of behaviour following 5-HT depletion could not be attributed to enhanced primary motivation as demonstrated by measures of food intake and latencies to collect food reinforcement. The lesion attenuated the increase of premature responding induced by high doses of systemically administered d-amphetamine. 5-HT depletion also attenuated the dose-dependent decrease in accuracy induced by (-)-sulpiride, a D2 receptor antagonist, although the effects of this drug on response latencies and premature responding were similar in both groups. However, the systemic administration of the D1 receptor antagonist, SCH 23390, blocked the impulsive responding produced by the lesion as indicated by a lack of lesion effects on the percentage of omitted trials and premature responding. The results suggest that central 5-HT depletion results in impulsive, fast responding, which nevertheless does not impair accuracy of visual discrimination performance. The increased impulsivity may be mediated by altered 5-HT-dopamine interactions, with the lesion removing an inhibitory influence over dopamine neurotransmission.

5,7-Dihydroxytryptamine↗

PubMed1997

Effect of central 5-hydroxytryptamine depletion on performance in the "time-left" procedure: further evidence for a role of the 5-hydroxytryptaminergic pathways in behavioural "switching".

This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance in a free-operant timing schedule: the "time-left" procedure. Rats received either injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained in a discrete trials schedule in which reinforcers were provided for responding on either of two levers, A and B. At a random time point, t s after the start of each trial, a response on A resulted in the delivery of one food pellet after dA s, whereas a response on B resulted in the delivery of two pellets after 60-t s. The value of dA was varied between 1 and 8 s in different phases of the experiment. Both groups showed decreasing response rates on lever A and increasing response rates on lever B as a function of time within the trial. An index of timing (T75: the time within the trial at which relative response rate on B attained a value of 75%) was systematically related to the value of dA, but did not differ significantly between lesioned and control rats. However, the lesioned group showed significantly higher rates of switching between response alternatives than the sham-lesioned group at all values of dA. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not significantly altered. The results provide further evidence that the ascending 5HTergic pathways may contribute to the inhibitory regulation of switching between behavioural states.

5,7-Dihydroxytryptamine↗

PubMed1999

Effect of central 5-hydroxytryptamine depletion on tolerance of delay of reinforcement: evidence from performance in a discrete-trials "time-left" procedure.

This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance on a new discrete-trials version of the "time-left" procedure. Rats received either injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained in a discrete trials schedule in which reinforcers were provided for responding on either of two levers, A and B. At a random time point, t s after the start of each trial, the two levers were inserted into the operant chamber: a response on A resulted in the delivery of one food pellet after dA s, whereas a response on B resulted in the delivery of two pellets after 84-t s. The value of dA was varied between 1 and 12 s in different phases of the experiment. Both groups showed an increasing tendency to respond on lever B as a function of time within the trial. Logistic functions were fitted to the data from each group, and a value of the "indifference point" (T50: the time within the trial at which proportional choice of B attained a value of 50%) was derived for each rat. For each value of dA, the values of T50 were significantly greater in the lesioned rats than in the control rats, reflecting a rightward shift of the logistic function in the lesioned group. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not significantly altered. The results provide further evidence for the involvement of the ascending 5HTergic pathways in the control of operant behaviour by delayed positive reinforcers.

5,7-Dihydroxytryptamine↗

PubMed1999

Effect of central 5-hydroxytryptamine depletion on performance in the free-operant psychophysical procedure: facilitation of switching, but no effect on temporal differentiation of responding.

This experiment examined the effect of destroying the ascending 5-hydroxytryptaminergic (5-HTergic) pathways on timing and switching behaviour in the free-operant psychophysical procedure. Rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for sucrose reinforcement; sessions consisted of fifty 50-s trials in which reinforcers were available on a variable-interval 30-s schedule. In the first 25 s, of each trial, reinforcement was only available for responses on lever A; in the last 25 s, it was available only for responses on lever B. In phase 1 (70 sessions) repetitive switching between the levers was prevented by withdrawal of lever A after the first response on lever B in each trial; in phase 2 (40 sessions) this constraint on switching was removed; in phase 3 (40 sessions) the constraint was reinstated. Data were collected from probe trials (four per session) in which no reinforcers were delivered, during the last ten sessions of each phase. In all phases, both groups showed declining response rates on lever A and increasing response rates on lever B as a function of time from the onset of the trial. Response rate on lever B, expressed as percentage of overall response rate, could be described by a two-parameter logistic function. Removal of the constraint on switching reduced the slope of the function without changing the indifference point (time corresponding to 50% responding on lever B). The parameters of the timing function did not differ between the groups in any of the phases. However, the lesioned group showed a greater enhancement of switching rate during phase 2 than the control group. The levels of 5-HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. The results provide further evidence for the involvement of the ascending 5-HTergic pathways in switching between response alternatives, but cast doubt on our previous suggestion that the effects of 5-HT depletion on temporal differentiation of behaviour are mediated by facilitated switching.

5,7-Dihydroxytryptamine↗

PubMed2001

Serotonin depletion attenuates cocaine seeking but enhances sucrose seeking and the effects of cocaine priming on reinstatement of cocaine seeking in rats.

RATIONALE: Acute serotonin (5-HT) depletion by the tryptophan hydroxylase inhibitor, para-chlorophenylalanine, attenuates cocaine seeking in rats. OBJECTIVE: The present study examined the effects of chronic 5-HT depletion on cocaine- and sucrose seeking using the 5-HT-selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). METHODS: Separate groups of rats were trained to lever press for cocaine infusions (0.33 mg/kg/0.1 ml, i.v.) or for sucrose pellets (45 mg Noyes) on a fixed ratio (FR) 1 schedule of reinforcement during daily 2-h sessions. Subsequently, animals received i.c.v. infusions of either vehicle or 5,7-DHT (150 microg/6 microl or 200 microg/20 microl). After a minimum of 10 days post-lesion, cocaine- and sucrose seeking were measured as lever presses in the absence of reinforcement (extinction). Some cocaine-trained animals were also assessed for the re-establishment of self-administration and reinstatement of extinguished cocaine seeking by i.v. cocaine priming injections and response-contingent presentations of cocaine-paired stimuli. RESULTS: 5-HT depletion by the 150 microg/6 microl dose of 5,7-DHT failed to alter cocaine- and sucrose seeking despite producing a 42-77% depletion of 5-HT in limbic terminal regions. The 200 microg/20 microl dose of 5,7-DHT attenuated cocaine seeking but enhanced sucrose seeking during extinction and produced a 55-85% depletion of 5-HT. In addition, cocaine-paired cues and cocaine priming reinstated cocaine-seeking behavior, and responding was enhanced in 5,7-DHT-treated animals relative to vehicle-treated controls at the 1 mg/kg/0.1 ml priming dose. However, re-establishment of cocaine self-administration was not altered by 5,7-DHT. CONCLUSION: The results suggest that 5-HT depletion may attenuate cocaine seeking but may enhance sucrose seeking when animals are tested during extinction. Furthermore, 5-HT depletion may enhance cocaine seeking produced by cocaine itself. Together these findings suggest that 5-HT depletion may have opposite effects on incentive motivation for cocaine during abstinence versus relapse.

5,7-Dihydroxytryptamine↗

PubMed2000

The 5-HT(1A) receptor agonist 8-OH-DPAT reduces rats' accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT(1A) receptors.

RATIONALE: Whilst several studies have investigated the role of serotonergic receptor subtypes in learning and memory, relatively few studies have examined their role in attentional processes. OBJECTIVE: The present study investigated the role of pre- and postsynaptic 5-HT1A receptors on rats' attentional performance in the five-choice serial reaction time task (5-CSRT). METHODS: Hungry rats were trained in the 5-CSRT task to detect brief (0.5 s) flashes of light presented randomly in one of five locations with a fixed intertrial interval of 5 s paced by the rat. We studied the effects of 8-OH-DPAT, a 5-HT1A receptor agonist, at various subcutaneous (SC) doses (10-100 microg/kg) on measures of rats' discriminative accuracy (the index of attentional functioning) and various behavioural indices of response control and motivation. Manipulations of basic task parameters, intracerebroventricular (ICV) injections of 5,7-dihydroxytryptamine (5,7-DHT) to deplete forebrain 5-HT and treatments with a selective 5-HT1A receptor antagonist WAY 100635 were made in order to determine the behavioural and neural specificity of the effects of 8-OH-DPAT. RESULTS: A dose of 100 microg/kg, but not lower doses, significantly reduced choice accuracy and increased errors of omission, latencies to respond correctly and to collect food reward and premature responses. All these effects were completely blocked by WAY 100635, injected SC 5 min before 8-OH-DPAT at doses from 10-100 microg/kg. WAY 100635 by itself had no effect in the task. Dimming the visual stimuli to one-third of the usual brightness did not modify the effect of 8-OH-DPAT on choice accuracy. Prolonging the stimuli from 0.5 to 1.0 s reversed 8-OH-DPAT's effect on choice accuracy but did not modify the other effects on rats' performance. An ICV injection of 150 microg 5,7-DHT, which depleted forebrain serotonin by 90%, reversed 8-OH-DPAT's effect on choice accuracy but did not modify the effects on errors of omission and latency to make correct responses. Similar effects were found by infusing 1.0 microg/0.5 microl WAY 100635 in the dorsal raphe 5 min before 8-OH-DPAT. 8-OH-DPAT increased the latency to collect the reinforcement; this effect was attenuated by ICV 5,7-DHT and completely antagonized by WAY 100635 in the dorsal raphe. Rats treated with 5,7-DHT or 8-OH-DPAT showed more premature responses and these effects were markedly reduced by the combined treatment. CONCLUSIONS: The results suggest that stimulation of presynaptic 5-HT1A receptors is involved in the ability of 8-OH-DPAT to cause attentional dysfunction and enhance impulsivity while slowing of responding and increase in errors of omission mainly depend on stimulation of post-synaptic 5-HT1A receptors.

5,7-Dihydroxytryptamine↗

PubMed1999

The influence of serotonin depletion on rat behavior in the Vogel test and brain 3H-zolpidem binding.

The influence of p-chlorophenylalanine (p-CPA) and 5,7-dihydroxytryptamine (5,7-DHT)-induced serotonin depletion on rat behavior as well as on zolpidem's the behavioral effects and binding to some brain areas of zolpidem, was examined with the help of Vogel's punished drinking test and autoradiography, respectively. Moreover, changes in the serotonin levels and turnover rate were studied in the forebrain and brainstem of rats pretreated with various ligands at the benzodiazepine (BDZ) receptors (midazolam, bretazenil, abecarnil, zolpidem). These drugs were given at doses shown previously to significantly disinhibit animal behavior suppressed by punishment in the Vogel test (Nazar et al., 1997). It was found that serotonin decrease in the frontal cortex and hippocampus after p-CPA significantly and inversely correlated with rat behavior controlled by fear in the VT. p-CPA produced an anticonflict activity in the absence of effect on spontaneous drinking, pain threshold and motility of animals. All applied benzodiazepine receptor ligands decreased the 5-HT turnover rate in the frontal cortex and hippocampus, whereas in the brainstem only abecarnil and zolpidem diminished 5-hydroxyindoleacetic acid levels. This part of the study replicated earlier data with neurotoxins and indicated that the anxiolytic-like effect of 5-HT depletion in some models of anxiety did not depend on changes in animal appetitive behavior or stimulus control. Moreover, the fact that all nonselective and selective (zolpidem) agonists of the type 1 benzodiazepine receptors seemed to produce the same anticonflict effect and decreasing 5-HT turnover indicates that this subtype of benzodiazepine receptor may be important for the interaction between brain 5-HT and GABA/BDZ systems. Accordingly, it was found that serotonin decrease enhanced the anticonflict effect of zolpidem in the Vogel test and increased 3H-zolpidem binding to the occipital cortex and substantia nigra. Altogether, the present study provides more arguments for the role of changes in the activity of brain 5-HT innervation in the control of emotional processes. Moreover, it points to the BDZ1 receptor subtype as a possible target of interaction between brain 5-HT and GABA(A)/BDZ systems.

5,7-Dihydroxytryptamine↗

PubMed2005

Aftereffects of microinjections of neurotensin into the substantia nigra of the brain on conditioned motor responses in rats with lesions to serotoninergic neurons.

The effects of neurotensin microinjections into the substantia nigra of the brain on the performance of motor reactions in response to positive (food reinforcement) and negative (unreinforced) conditioned signals were studied, along with the characteristic aftereffects of these microinjections in rats with lesions to serotoninergic neurons in the dorsal cervical nucleus. Lesions were produced by local administration of the selective neurotoxin 5,7-dihydroxytryptamine. Microinjections of neurotensin were found to weaken the disinhibitory effects of neurotoxin on extinction of intersignal responses and extinction of conditioned motor reactions in response to presentation of negative stimuli, but to have no marked effect on the performance of reactions evoked by positive conditioned signals. Changes persisted into subsequent experiments without peptide microinjections. Measurements of the level of preference of the animals for one quadrant of the experimental chamber showed that operated rats avoided occupying the test quadrant and preferred to locate themselves in the opposite quadrant. Neurotensin released this effect of the neurotoxin. These results lead to the conclusion that these behavioral effects of neurotensin are associated with its normalizing influences on the motivational-emotional state of the animals with lesions to serotoninergic neurons and may also be due to the formation in the animals of a contextual conditioned emotional state, which aids optimization of the adaptive functions of the brain.

5,7-Dihydroxytryptamine↗

PubMed1986

Pharmacological analysis of the neurotransmitter mechanisms regulating phenylethanolamine N-methyltransferase in the adrenal gland.

The i.p. administration of reserpine daily for 4 days to rats brought about an increase of adrenal phenylethanolamine N-methyltransferase (PNMT) activity. However, the combination of the systemic administration of p-chlorophenylalanine (PCPA) and reserpine for 3 days produced an earlier increase in this adrenal enzyme. The effect was reduced significantly in the denervated gland. Prior administration of 5,7-dihydroxytryptamine (DHT) i.c.v. to rats greatly potentiated the inducing effect of reserpine. On the other hand, the depletion of catecholamines by giving rats alpha-methyl-p-tyrosine (AMPT) i.p. or 6-hydroxydopamine (6-OHDA) i.c.v. did not alter the action of reserpine on adrenal PNMT. PCPA, DHT, AMPT and 6-OHDA did not have any effect by themselves on adrenal PNMT, but the combination of PCPA and AMPT, each given i.p., caused increased adrenal PNMT activity. The administration of dopamine agonists, a treatment that increases adrenal TH, did not modify adrenal PNMT. We conclude that the induction of PNMT by reserpine involves depletion of catecholamines and serotonin, the depletion of serotonin having the more powerful effect. A monoaminergic (serotonergic) inhibitory pathway is involved in the central regulation of adrenal PNMT activity.

Adrenal Glands↗

PubMed1975

Disappearance of supra-ependymal 5-HT axons in the rat forebrain after electrolytic and 5,6-DHT-induced lesions of the medial forebrain bundle.

The present study was intended to demonstrate the origin of supra-ependymal 5-hydroxytryptamine axons in the rat forebrain. Electrolytic lesions and injections of 5,6-dihydroxytryptamine (10 mug in 4 mul) were carried out unilaterally in and close to the medial forebrain bundle in the posterior hypothalamus of rats. Ten to 14 days later, terminal axons and formaldehyde-induced indolealkylamine fluorescence had virtually disappeared supra-ependymally in the lateral ventricles and interventricular foramina ipsilateral to the lesion if the indolealkylamine axons passing through the medial part of the medial forebrain bundle had been destroyed. No changes were observed, electron microscopically or fluorescence histochemically, in ventricles contralateral to the lesion. It is concluded that the supra-ependymal serotonergic nerve terminals in the lateral ventricles and interventricular foramina originate, uncrossed, from non-terminal axons passing through the medial forebrain bundle in the posterior hypothalamus.

5,6-Dihydroxytryptamine↗

PubMed1977

Serotonergic afferents to the dorsal raphe nucleus: evdience from HRP and synaptosomal uptake studies.

Afferent connections of the serotonin (5-HT)-containing dorsal raphe nucleus were investigated in the rat utilizing the horseradish peroxidase (HRP) retrograde cell labeling technique. Small quantities (0.1-0.5 mul) of HRP solutions were infused into the dorsal raphe, and the brains were examined 19-72 h later for retrograde transport of the enzyme. Intrinsic connections within the dorsal raphe nucleus were revealed by this mapping technique, as was an input to the dorsal raphe from another serotonergic cell group, the median raphe nucleus. Little evidence was found for projections from other, more remote, brain sites. A serotonergic innervation of the dorsal raphe was also demonstrated by the presence of high affinity uptake of [3H]5-HT (Km=0.17 muM) into synaptosomal suspensions of the dorsal raphe nucleus. Synaptosomal uptake of [3H]5-HT was blocked by selective destruction of serotonergic axon terminals induced by the intraventricular injection of 200 mug of 5,7-dihydroxytryptamine following desipramine HCl pretreatment, but not by destruction of catecholaminergic axon terminals induced by intraventricularly injected 6-hydroxydopamine (2 X 250 mug). The uptake of [3H]-5-HT by synaptosomes of the dorsal raphe was comparable to that of striatal and hypothalamic synaptosomes, and markedly greater than that of synaptosomes from the cerebellum or nearby dorsal central gray or midbrain reticular formation, indicating the presence of a relatively dense serotonergic innervation. These data together indicate that neurons in the dorsal raphe nucleus receive a prominent serotonergic input that is derived, at least in part, from other neurons within the dorsal nucleus and from a neighboring raphe nucleus.

5,6-Dihydroxytryptamine↗

PubMed1977

Food intake and body weight: effects of specific and non-specific lesions in the midbrain path of the ascending noradrenergic neurons of the rat.

Bilateral injections of 4.8 or 12 microgram of 6-hydroxydopamine hydrobromide were made in the midbrain path of the ascending norepinephrine (NE) fibers. Maximum NE depletion was obtained with the 4 microgram dose. Increasing the dose did not increase NE depletion in either the hypothalamus or the telencephalon. Increases in food intake were observed following the 12 microgram dose only. Electrolytic, copper sulfate, or 5,6-dihydroxytryptamine lesions at the same site caused increases in both food intake and body weight with only moderate (-32 to -58%) decreases in NE levels. Behavioral changes were seen in only those groups in which a large amount of non-specific tissue damage was also observed. Therefore, the behavioral effects were attributed to general tissue damage in the area and not the NE fibers specifically.

5,6-Dihydroxytryptamine↗

PubMed1979

Denervation supersensitivity to serotonin in rat forebrain: single cell studies.

To investigate the development of denervation supersensitivity to serotonin (5-hydroxytryptamine, 5-HT) in the amygdala (AMYG) and the ventral lateral geniculate nucleus (vLGN), single cell recordings, microiontophoretic, histochemical and biochemical techniques were used in the present study. 5-HT projections to the vLGN and the AMYG were destroyed by 5,7-dihydroxytryptamine (5,7-DHT, a relatively selective toxin for 5-HT neurons) injected directly into the lateral ventricle or the ascending 5-HT pathway in the ventromedial tegmentum area. Enhanced responsiveness of cells to the inhibitory effect of microiontophoretically applied 5-HT (ionto-5-HT) began to develop within 24 h and approached a maximum 7 days after 5,7-DHT pretreatment. In general, the time courses for the reduction in both the density of 5-HT fluorescent varicosities and synaptosomal 5-HT uptake activity paralleled the time course for the development of denervation supersensitivity to 5-HT. During the first 2 days after 5,7-DHT, the enhanced sensitivity was selective for 5-HT; responses to D-lysergic acid diethylamide (LSD), norepinephrine (NE) and gamma-aminobutyric acid (GABA) were unchanged. Seven or more days after 5,7-DHT there was a marked increase of the responsiveness of neurons in the vLGN and the AMYG to both 5-HT and LSD (a 5-HT agonist which is not a substrate for the high affinity 5-HT uptake system). At these later times, the responsiveness of cells in the AMYG to NE and to a lesser extent GABA was also increased. In contrast to the marked supersensitivity seen after 5,7-DHT induced denervation, chronic administration of parachlorophenylalanine, a 5-HT synthesis inhibitor, failed to induce 5-HT supersensitivity.

5,7-Dihydroxytryptamine↗

PubMed1979

Facilitation of memory consolidation by vasopressin: mediation by terminals of the dorsal noradrenergic bundle?

Administration of arginine-vasopressin (AVP, 5 micrograms, s.c.) immediately after the learning trial results in a long-term facilitation of a one-trial learning passive avoidance response. This effect of AVP is absent in animals with prior destruction of the ascending dorsal noradrenergic bundle by bilateral microinjection of 6-hydroxydopamine (6-OHDA). Postlearning local microinjection of a minute amount of AVP via chronically implanted cannulae into the locus coeruleus did not influence passive avoidance behavior. Upon injection into the midbrain dorsal raphe nucleus, however AVP facilitated passive avoidance behavior. This effect, however, was absent in rats receiving previous microinjection of 5,6-dihydroxytryptamine (5,6-DHT) or of 6-OHDA into the dorsal raphe nucleus. Bilateral 6-OHDA-induced lesions of the nucleus accumbens or 5,6-DHT-induced destruction of the dorsal raphe nucleus did not prevent the effect of AVP administered subcutaneously. The data suggest that vasopressin facilitates memory consolidation processes by modulating noradrenergic neurotransmission in terminals of the dorsal noradrenergic bundle. The serotoninergic neuronal network originating from the dorsal raphe nucleus has a secondary--norepinephrine-mediated--influence upon these processes.

5,6-Dihydroxytryptamine↗

PubMed1979

The role of locus coeruleus in decapitation convulsions of rats.

The role of the central norepinephrine (NE) system, especially the locus coeruleus (LC), in the occurrence of decapitation convulsions was investigated in rats. Intraspinal injection of 6-hydroxydopamine (6-OHDA) caused a significant inhibition of decapitation convulsions as shown by prolongation of the latency and shortening of the convulsion's duration, as well as decreasing the NE content of the spinal cord to 35% of the control value without affecting the NE content of the various regions in the brain. Chemical lesion of the descending bundle from the LC by treatment with 6-OHDA significantly inhibited decapitation convulsions in a similar manner. Moreover, there was a decrease in the NE content of the spinal cord and hypothalamus to 24% and 47% of the control value, respectively. Bilateral electrolytic lesion of the LC also significantly inhibited decapitation convulsions and decreased the NE content of the cortex and spinal cord to 15% and 74% of the control value, respectively. However, lesions of the dorsal and ventral NE bundle by treatment with 6-OHDA, which caused a marked decrease in the NE content of the cortex and hypothalamus, respectively, did not affect the decapitation convulsion. Intraspinal injection of 5,6-dihydroxytryptamine resulted in a decrease in the 5-hydroxytryptamine content of the spinal cord only; moreover, it did not change the decapitation convulsion. These results suggest that coeruleospinal NE neurons play an important role in the occurrence of decapitation convulsions.

5,6-Dihydroxytryptamine↗

PubMed1980

Septal elicitation of hippocampal theta rhythm after localized de-afferentation of serotoninergic fibers.

Previous experiments using serotonin antagonists and electrolytic raphe lesions suggest that the serotonergic input to the hippocampus inhibits low frequencey (< Hz) theta rhythm in the rat, whereas experiments using raphe stimulation suggest facilitation. The present experiments employed neurotoxic lesions of the serotonergic input to the hippocampus in an attempt to reproduce the effects of systemically administered antagonists. If the septal area is stimulated at frequencies between 6 and 10 Hz in the rat, the threshold current for driving hippocampal theta is minimum at 7.7 Hz. Systemic blockage of serotonergic synapses has been shown to shift this minimum to 6.9 Hz. In the present experiments, neurotoxic lesions were made with injections of 5,7-dihydroxytryptamine into the cingulum bundle, fornix or both. The observed effect depended on the loss of serotonin in the hippocampus, rather than the site of injection, and extensive depletion shifted the minimum to 6.9 Hz. These results indicate that the fornix and cingulum serotonergic inputs to the hippocampus are functionally homogenous, at least with respect to this response; and that the effects of systemic manipulation of serotonin systems on the septal elicitation of hippocampal theta rhythm may be attributed to changes in these two inputs.

Afferent Pathways↗

PubMed1980

Resting and K+-evoked release of serotonin and norephinephrine in vivo from the rat and cat spinal cord.

Using a spinal superfusion system, the release of serotonin (5-HT) and norepinephrine (NE) from rat and cat spinal cord was measured using a high performance liquid chromatograph with an electrochemical detector. Resting levels of 5-HT and NE in the chloralose-urethanized rat were of the order of 0.8 and 0.4 ng/ml, respectively. Potassium (40 or 80 mM, in excess) produced a dose-dependent increase in the levels of both monoamines in the superfusate. The substitution of cobalt blocked this evoked release. Depletion of spinal 5-HT or NE by the prior intrathecal administration of 5,6-dihydroxytryptamine (5,6-DHT) or 6-hydroxydopamine (6-OHDA) reduced the resting levels of 5-HT and NE, respectively, and prevented the increase produced by excess potassium. These experiments indicate the ability to reliably collect and measure monoamines which overflow from spinal terminals and which reflect the degree of activation of the spinal monoamine system.

5,6-Dihydroxytryptamine↗

PubMed1980

Effect of noradrenaline and 5-hydroxytryptamine depletion on locomotion in the cat.

It has recently been hypothesized that stimulation of the mesencephalic locomotor region (MLR) can give rise to locomotion in mesencephalic cats due to activation of descending monoaminergic pathways to the spinal cord. This notion is based on the findings that monoamine agonists and precursors can induce hindlimb stepping in acute low spinal animals, and on the similarities between the effects of the noradrenaline (NA) precursor, L-DOPA, and stimulation of the MLR. The hypothesis that the descending monoamine systems comprise the only pathways which control the initiation of locomotion has been tested in the present study. NA was depleted from the CNS using intraspinal and intraventricular injections of 6-hydroxydopamine and i.v. injections of the NA synthesis inhibitor, alpha-methyltyrosine. Depletion of 5-hydroxytryptamine (5-HT) was achieved using intraventricular injections of 5,6-dihydroxytryptamine and i.p. p-chlorophenylalanine. These treatments did not abolish evoked locomotion in spite of substantial depletion of NA and 5-HT in the spinal cord and brain stem (maximal depletions of NA up to 14% of control in lumbar cord and 16% of control in pons; maximal depletions of 5-HT up to 19% of control in sacral cord and 25% of control in medulla). Combined depletion of NA and 5-HT did not abolish evoked locomotion in mesencephalic cats, although the treated animals displayed pronounced ataxia prior to decerebration. Depletion of NA or 5-HT alone did not alter locomotion in otherwise intact animals. A previous report that phenoxybenzamine antagonizes the effects of MLR stimulation was not confirmed. The results therefore do not support the hypothesis that descending pathways containing monoamines are essential for locomotion evoked by brain stem stimulation.

5,7-Dihydroxytryptamine↗