SEARCH · PubMed Health

Results for “Dihydroxytryptamines”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources

PubMed1982

Interaction of the median raphe nucleus and hypothalamic serotonin with cholinergic agents and pressor responses in the rat.

Experiments were performed to determine whether the pathway by which median raphe stimulation increases blood pressore involves serotonergic terminals in the anterior hypothalamic/preoptic area and cholinergic terminals in the posterior hypothalamus. Injection of 5,7-dihydroxytryptamine into the median raphe nucleus decreases serotonin and turnover of acetylcholine in the hypothalamus of the rat. The hypertensive action of injection of serotonin into the anterior hypothalamic/preoptic area is blocked by injection of atropine or hemicholinium-3 into the posterior hypothalamus and by i.c.v. injection of hemicholinium-3 when measured in urethane-anesthetized rats. However, the pressor effect of electrical stimulation of the median raphe nucleus is not blocked by the intrahypothalamic injection of atropine or hemicholinium-3, only partially blocked by i.c.v. hemicholinium-3 and not blocked by specific lesioning with 5,7-dihydroxytryptamine. Moreover, injection of metergoline into the anterior hypothalamic/preoptic area blocks the pressur response to hypothalamic serotonin but does not block the pressor response to median raphe stimulation. Stimulation of the median raphe nucleus does not affect acetylcholine turnover in the hypothalamus. These results suggest that serotonergic mechanisms in the anterior hypothalamic/preoptic area exert their pressor effect through a pathway with a cholinergic link in the posterior hypothalamus. Serotonergic neurons arising in the median raphe nucleus probably are not involved in this pathway through the hypothalamus, although a cholinergic pathway may be involved elsewhere in their pressor actions. The effect of median raphe nucleus lesion on turnover of acetylcholine in the hypothalamus is most likely unrelated to regulation of blood pressure.

Acetylcholine↗

PubMed1977

Cortical effects of the electrical stimulation of the locus coeruleus.

The results of the electrical stimulation of the locus coeruleus in curarized cats, and the effects upon the observed cortical responses of 5,6-dihydroxytryptamine or 6-hydroxydopamine injected intracisternally or applied in the subarachnoideal space were studied. The changes were followed on the strychnine spikes produced after the topical application of this drug. Stimulation of the locus coeruleus elicited a response in every area of the cortex explored. The response was complex, showed a phase of depression and a phase of enhancement both mixed in different proportions. The depressant reaction was more marked with lower strengths of stimulation and the enhancement reactions appeared more evident with the stronger stimuli. Both these reactions were blocked by the previous administration of 6-hydroxydopamine and only the depressant one was practically abolished by 5,6-dihydroxytryptamine. It is concluded that a complex interaction exists between the noradrenergic neurons of the locus coeruleus and the serotonergic neurons, probably those of the raphe nuclei. It is suggested that the axons of the noradrenergic neurons in their way to the cortex, give off collaterals that innervate some serotonergic neurons. The monoamines liberated by these axon terminals at the cerebral cortex would act as neurohumoral agents.

Animals↗

PubMed1980

Effects of indolic neurotoxins on enteric serotonergic neurons.

The effects of the indolic neurotoxins 5,6- and 5,7-dihydroxytryptamine (5,6-DHT; 5,7-DHT) on the enteric nervous system were examined. 5,6-DHT, in moderate dosage, 40 mg/kg, decreased uptake of tritiated 5-hydroxytryptamine (3H-5-HT) but not that of tritiated norepinephrine (3H-NE). However, selectivity of the neurotoxins for enteric serotonergic rather than adrenergic axons was enhanced by pretreating animals with desmethylimipramine to inhibit the catecholamine uptake mechanism. When this was done, 5,7-DHT was found to prevent the development of 5-HT histofluorescence (following injection of L-tryptophan) without affecting histofluorescence of NE. In contrast, 6-hydroxydopamine virtually abolished NE histofluorescence and uptake of 3H-NE without affecting development of 5-HT histofluorescence or uptake of 3H-5-HT. Electron microscopy revealed that b,7-DHT induced dose-dependent lesions of axonal varicosities in the enteric nervous system. Early lesions, 1--4 hours following injection, resembled cytolysosomes and consisted of membrane enclosed regions of opaque cytoplasm containing synaptic vesicles. Affected varicosities contained a mixed population of large dense cored (approximately 120 nm) and small lucent vesicles (approximately 70 nm) but none exhibited pre- or postsynaptic membrane specializations. After 24 hours terminals degenerated and were engulfed by surrounding supporting cells. It is concluded that peripheral serotonergic neurons resemble central serotonergic neurons in susceptibility to the toxic effects of indolic neurotoxins. These neurotoxins are useful anatomical markers of serotonergic terminal varicosities.

5,6-Dihydroxytryptamine↗

PubMed2002

7-Hydroxytryptophan, a novel, specific, cytotoxic agent for carcinoids and other serotonin-producing tumors.

BACKGROUND: Carcinoids and small cell lung carcinomas stimulate their growth in an autocrine manner by releasing serotonin, an effect that is blocked by selective serotonergic receptor antagonists that, unfortunately, exert undesirable side effects on serotonergic central nervous function. Moreover, conventional chemotherapeutic agents, such as streptozocin, fluorouracil, cyclophosphamide, and doxorubicin, which target tumor cells directly, have produced disappointing results in the treatment of patients with these tumors in the advanced stage. Therefore, there is still a need for more specific and potent chemotherapeutic agents in the fight against serotonin-producing tumors. METHODS: The authors synthesized 7-hydroxytryptophan to test its chemotherapeutic value in cell culture, using a system consisting of serotonin-producing and nonproducing cell lines. RESULTS: The authors chose tryptophan hydroxylase, the rate-limiting enzyme of serotonin biosynthesis, which is expressed highly in small cell lung carcinomas and carcinoids, as a target for the induction of cellular suicide by chemotherapy. They found that this otherwise substrate specific enzyme was capable of metabolizing in situ a harmless tryptophan analogue, 7-hydroxytryptophan, to a potent toxin, 5,7-dihydroxytryptamine, a conversion blocked by the specific tryptophan hydroxylase inhibitor parachlorophenylalanine. CONCLUSIONS: These data suggest that 7-hydroxytryptophan may be a highly specific chemotherapeutic compound against serotonin-producing tumors that also interferes with the autocrine capabilities of serotonin synthesis.

5,6-Dihydroxytryptamine↗

PubMed1989

Connections of indoleamine-accumulating cells in the rabbit retina.

To study the connections of the neurons of the rabbit retina that accumulate indoleamines, we injected 5,7-dihydroxytryptamine into the vitreous body. It accumulated within a subset of amacrine cells and could be visualized there by aldehyde-induced fluorescence. The fluorescent labeling was photo-converted to an insoluble, osmiophilic product by irradiation in the presence of diaminobenzidine, and the tissue was examined by electron microscopy. Preservation of the structure of the tissue after photoconversion was satisfactory and the dendrites of the indoleamine-accumulating cells could easily be identified. They form a dense plexus near the junction of the inner plexiform and ganglion cell layers, where they exhibit large synaptic endings that occupy a substantial fraction of the surface of rod bipolar terminals. The dendrites of the indoleamine-accumulating cells receive input from rod bipolars at dyad synapses, where the other postsynaptic partner is a dendrite of a narrow-field, bistratified amacrine cell; in addition, they receive amacrine cell input throughout the inner plexiform layer. The only outputs we observed are reciprocal synapses onto the rod bipolar endings. Thus, these amacrine cells appear to exert an important effect on the transmission of scotopic information through the retina.

5,7-Dihydroxytryptamine↗

PubMed1989

Monoamine-accumulating ganglion cell type of the cat's retina.

A monoamine-accumulating ganglion cell type has been identified in an in vitro preparation of the cat's retina by a catecholamine-like fluorescence that appears following intravitreal injections of dopamine and the indoleaminergic transmitter analog, 5,7-dihydroxytryptamine (5,7-DHT). A subpopulation of large, weakly fluorescing neurons were identified as composing a single, morphologically distinct ganglion cell type by intracellular injections of horseradish peroxidase (HRP). In a sample of 374 HRP-filled cells soma diameter ranged from 13-21 microns (mean +/- SD = 16.6 +/- 1.3). Dendritic field size increased with increasing retinal eccentricity from 150-200 microns diameter at 0.5 mm from the area centralis to 600-800 microns diameter in the far retinal periphery. Dendrites are thin (approximately 1 micron diameter), show a characteristic branching pattern, and are narrowly stratified at the outer border of the inner plexiform layer. The monoamine-accumulating ganglion cell and the outer (OFF-center) alpha cell occupy distinct strata within sublamina a of the inner plexiform layer separated by a gap of about 5 microns. The total number of monoamine-accumulating (MA) ganglion cells was estimated at 5,400, about 3.5% of the total ganglion cell population. Spatial density of the MA ganglion cells, calculated from cell counts made in vitro, ranges from 60 cells/mm2 near the area centralis to 5 cells/mm2 in the far retinal periphery. A coverage factor (density x dendritic field area) of 2.2 was maintained from central to peripheral retina. The nature of the dendritic overlap was observed directly by making HRP injections into several neighboring ganglion cells. Five to seven neighboring dendritic trees extensively overlapped a given cell's dendritic field. However the dendritic processes did not intersect randomly but tended to interdigitate such that a uniform interdendritic spacing and density of dendritic processes was constructed locally within the dendritic plexus. Rotation of individual dendritic trees from their normal orientation produced a dramatic 4-5-fold increase in the number of dendritic intersections, suggesting that an active, local mechanism operates in the precise placement of individual dendrites within the plexus. The monoamine-accumulating ganglion cell appears morphologically equivalent to the delta ganglion cell (Boycott and Wässle; J. Physiol. (Lond.) 240:397-419, '74; Kolb et al.; Vision Res. 21:1081-1114, '81) and to the recently recognized indoleamine-accumulating ganglion cell (Wässle et al: J. Neurosci. 7:1574-1585, '87).(ABSTRACT TRUNCATED AT 400 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1986

GM1 ganglioside counteracts selective neurotoxin-induced lesion of developing serotonin neurons in rat spinal cord.

The effect of exogenous monosialoganglioside GM1 on neurotoxin-induced lesioning of bulbo-spinal serotonergic neurons of newborn rats was studied by means of biochemical and immunocytochemical techniques. 5,7-dihydroxytryptamine (5,7-HT, a selective serotonin neurotoxin) treatment of newborn rats caused a pronounced reduction of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the thoracic and lumbar spinal cord, while an increase of 5-HT and 5-HIAA was found in the pons medulla. These biochemical alterations were regionally correlated with similar changes in 5-HT nerve terminal density analyzed by image analysis. GM1 administration (30 mg/kg for 4 consecutive days) antagonized the reduction of 5-HT and 5-HIAA levels induced by 5,7-HT treatment in the lumbar spinal cord of 2-month-old rats, as well as the decrease of 5-HT nerve terminal density in both thoracic and lumbar spinal cord of 1- and 2-month-old rats. A minor counteracting effect of GM1 was found in the pons medulla where the neurotoxin induced an increase of 5-HT and 5-HIAA levels. These data support the hypothesis that GM1 may have a preventing action on retrograde degenerative processes following chemical lesion and/or a growth-stimulating effect on injured 5-HT neurons.

5,7-Dihydroxytryptamine↗

PubMed1987

Effect of spinal cord TRH deficiency on lower motorneuron function in the rat.

Thyrotropin-releasing hormone (TRH), present in high concentrations in the mammalian spinal cord, exerts excitatory effects on the alpha-motorneuron (AMN) via axodendritic contacts. We used the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) to deplete TRH from the ventral horn of the spinal cord of adult rats to determine whether the tripeptide may be trophic to the AMN. The rats were studied blindly and sequentially for 11 weeks. Motor performance remained normal by clinical and electrophysiologic assessments. AMN counts were not reduced in the lumbar cord, and gastrocnemius muscle showed no evidence of denervation in treated rats. We conclude that in the adult rat chronic ventral horn TRH deficiency does not lead to AMN degeneration and is not associated with a significant alteration of AMN function.

5,7-Dihydroxytryptamine↗

PubMed1984

Quantitative effects of a neurotoxin upon serotonin levels within tissue compartments of the medicinal leech.

The serotonin (5-hydroxytryptamine, 5-HT) content of tissue compartments in the medicinal leech, Hirudo medicinalis, was measured by means of high-pressure liquid chromatography coupled with electrochemical detection (HPLC-EC). Each segmental ganglion contains 21.3 +/- 2.9 (9) pmol 5-HT [X +/- SEM (N)]. The pharynx contains 7.1 +/- 1.1 (9) pmol 5-HT/mg wet weight; the salivary glands 3.2 +/- 0.9 (10), ventral body wall 2.0 +/- 0.2 (11), and vasofibrous tissue 1.2 +/- 0.2 (11). The blood of hungry leeches contains 8.7 +/- 1.9 (7) nM 5-HT while that of well-fed leeches is 2.2 +/- 0.4 (6) nM. Leeches were injected with the cytotoxic analog of serotonin, 5,7-dihydroxytryptamine (5,7-DHT) producing selective lesions of the peripherally projecting serotonin-containing neurons, and which in turn abolished their feeding behavior. The serotonin content of the pharynx and ganglia of these toxin-treated leeches were lowered significantly. The serotonin levels within the body wall and salivary glands were not altered significantly by the toxin treatment, but the levels within the vasofibrous tissue and blood were elevated substantially.

5,7-Dihydroxytryptamine↗

PubMed1986

Transient depletion of serotonin in the nervous system of Helisoma.

The present study shows that the drug 5,7-dihydroxytryptamine (5,7-diHT) can be used reliably to deplete the neurotransmitter serotonin (5-HT) from the nervous system of the snail Helisoma. The depletion is more effective in axonal and synaptic regions (85-90%) than in the somata (55%), is reasonably specific for serotonin (dopamine is affected to a much lesser extent), and is transient, with normal levels of neurotransmitter being restored by 2 months. A physiological correlate of 5-HT depletion has been shown in that an EPSP elicited by a cerebral serotonergic neuron (C1) onto a buccal motoneuron (B19) is much smaller during depletion and also recovers with time as 5-HT regains normal concentration. Despite the severe 5-HT depletion and physiological impairment, the gross morphology of neuron C1 remains indistinguishable from controls. Serotonergic depletion is not accompanied by development of receptor supersensitivity nor by the production of serotonin in extraneuronal sources.

5,7-Dihydroxytryptamine↗

PubMed1989

Similarities between aberrant serotonergic fibers in the aged and 5,7-DHT denervated young adult rat brain.

Recent morphological observations have suggested neurotransmitter specific degeneration of amongst others, the serotonergic system in the aged rat brain. However, morphological studies can only give a static picture of the events that take place over a period of several months. In the present study we used an experimental model in which degeneration of the serotonergic system in the young adult rat brain was produced on a short time scale. Morphological changes were studied 2 h and 1 or 14 days after intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT). Non-specific damage and severe depletion of serotonergic fibers was observed in the immediate surroundings of the injection site, representing the effects of high local concentrations of 5,7-DHT. Sometime after injection swollen varicosities and dilated non-varicose fibers were observed. Fourteen days after the 5,7-DHT treatment cluster-like fibers appeared. It is argued that these swollen and crumpled fiber knots are slowly degenerating fibers. A comparison is made with the abnormal serotonergic fibers in the aged rat brain and it is concluded that these aged abnormal fibers represent axonal degeneration of the serotonergic system in the senescent rat brain.

5,7-Dihydroxytryptamine↗

PubMed1984

Evidence against the involvement of serotonergic neurons in the anti-punishment activity of diazepam in the rat.

The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 microgram in 0.4 microliter) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 micrograms in 0.5 microliter) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10(-5)-10(-4)M in 0.2 microliter) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.

5,7-Dihydroxytryptamine↗

PubMed1989

A comparison of four techniques for mapping the distribution of serotonin and serotonin-containing neurons in fixed and living ganglia of the snail, Lymnaea.

The distribution of serotonin and serotonin-containing neurons was studied in the ganglia of the CNS of the snail Lymnaea stagnalis. Results of the application of three different labelling techniques on wholemount preparations were compared with each other and with the serotonin content of the ganglia, measured by high-performance liquid chromatography. Serotonin immunocytochemistry resulted in the highest number of labelled neurons, but the more recently developed in vivo method of 5,6- or 5,7-dihydroxytryptamine-induced pigmentation also proved to be a reliable technique for the visualization of serotonin-containing cell bodies. In comparison with these two techniques, the glyoxylic acid fluorescence method appeared to be less sensitive. The distribution and number of serotonin-containing neurons and biochemically measured serotonin in specific ganglia showed a close correlation. By combining the results of the three labelling techniques, a detailed map of serotonin-containing neurons was constructed, and this was compared with maps of identified neurons prepared from earlier electrophysiological studies. Previously described serotonergic neurons were consistently found, as well as several new serotonin-containing cell types in the cerebral, visceral and parietal ganglia. A network of serotonin-containing inter- and intraganglionic axon tracts, and thin serotonergic fibres in the perineurium were also demonstrated. This in vivo and in vitro identification of serotonin-containing neurons will facilitate further neurophysiological analysis of serotonergic neural mechanisms in Lymnaea.

5,6-Dihydroxytryptamine↗

PubMed1988

Mechanisms by which the putative serotonin receptor antagonist metitepin alters nociception in mice.

The putative serotonin (5-HT) receptor antagonist metitepin (0.5 mg/kg, intraperitoneally) produced hypoalgesia in the increasing temperature hot-plate test and hyperalgesia in the tail-flick test in mice. The effects of metitepin were not altered after depletion of 5-HT by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 80 micrograms free base, intracerebroventricularly) or the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA, 400 mg/kg for 10 consecutive days). After chronic administration (2 or 5 mg/kg for 18 consecutive days) tolerance to the effect of metitepin (0.5 mg/kg) and cross-tolerance to the antinociceptive effect of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 3 mg/kg) was found in the hot-plate test but not in the tail-flick test. It is suggested that metitepin may block descending 5-HT transmission while more complex mechanisms of action are involved at supraspinal level. One possibility is that metitepin exhibits partial agonist properties or, alternatively, that the drug may block 5-HT subsystems which tonically enhance nociception.

5,7-Dihydroxytryptamine↗

PubMed1984

Catecholamines and serotonin in the rat central nervous system after 6-OHDA, 5-7-DHT and p-CPA.

The norepinephrine (NE), epinephrine (EPI), dopamine (DA) and serotonin (5-HT) contents were measured radioenzymatically in seven anatomically defined regions (frontal cerebral cortex, hippocampus, hypothalamus, midbrain, pons-medulla oblongata, cerebellum and spinal cord) in adult normal animals, after treatment with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (p-CPA), and after the intraventricular administration of either 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT). The effects of p-CPA seemed not restricted to 5-HT, since reductions in catecholamine (CA) content were detected in several regions. After 5,7-DHT given under desimipramine (DMI) protection, comparable reductions in 5-HT levels were obtained but the changes in CA were less severe than after p-CPA. The neurotoxin 6-OHDA decreased the CA in all regions but also 5-HT content in hippocampus, hypothalamus and pons-medulla. The significance and the interpretation of these changes are discussed in relation to the specificity of the drugs employed, together with an assessment of the local monoamine turnover and the possible functional effects of monoamine interactions in the CNS.

5,7-Dihydroxytryptamine↗

PubMed1986

Enhanced selective 5-HT depletions in the DHT rat model: denervation supersensitivity and recovery of function.

The effects of enhancing 5-HT depletion with multiple intracisternal injections of 5,7-dihydroxytryptamine (DHT) on spontaneous or L-5-hydroxytryptophan (5-HTP)-induced behaviors (videotaped) and locomotor activity (photocell recording) were studied in the adult rat. After four DHT injections, 5-HT content in septum/accumbens, hippocampus, striatum, neocortex, cerebellum, and cervical spinal cord fell to 0-10% of controls. Multiple injections also significantly improved depletions in brainstem and diencephalon, which were not as extensive. Spontaneous locomotor activity (LMA) was increased in DHT-lesioned rats for 1 week. The associated behavioral abnormalities, hindlimb hyperextension and incomplete rearing were also transient and differed from the motor syndrome evoked by 5-HTP. Multiple DHT injections did not qualitatively modify the 5-HTP syndrome but shifted the dose response curve to the left compared to single injections. Syndrome behaviors shared a similar dose threshold and could be evoked with 30 mg/kg 5-HTP. Two weeks after DHT, the locomotor response to 5-HTP (65 mg/kg) was method dependent or biphasic: decreased in brief recordings when syndrome abnormalities were greatest and increased in hour-long recordings. LMA correlated with rearing in controls and inversely with total behavioral abnormality in DHT-lesioned rats injected with 5-HTP. Multiple regression of LMA with regional 5-HT content was significant for hippocampus, striatum, and septum/accumbens. These data suggest that the development of denervation supersensitivity, the proposed mechanism of the 5-HTP-evoked motor syndrome, may be responsible for the rapid recovery of function in LMA.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1978

Biochemical and behavioral effects of serotonin neurotoxins on the nigrostriatal dopamine system: comparison of injection sites.

Unilateral injections of the serotonin neurotoxin, 5,7-dihydroxytryptamine (DHT), at various points along the 5-HT pathway to the forebrain produce a turning syndrome associated with alterations of dopamine synthesis in the ipsilateral striatum. Unilateral injections of DHT into the SN produced an ipsilateral increase in striatal dopamine (DA) turnover and contralateral rotation in response to amphetamine or apomorphine. Injection of DHT into the MFB produced an ipsilateral decrease in striatal DA turnover and tyrosine hydroxylase (TOH) activity, and ipsilateral rotation in response to amphetamine or apomorphine. After the injection of DHT into the SN or MFB, there was a significant correlation between the rates of drug-induced rotation, the decrease in cortical 5-HT turnover, and the change in striatal DA turnover, suggesting that the unilateral change in DA turnover (and, presumably, the increased stimulation of DA receptors) is causally linked to turning. Injection of DHT into the zones of the striatum and GP richest in 5-HT terminals produced the same responses as the MFB-lesioned rats: ipsilateral rotation and a decrease in striatal TOH activity. Injection of DHT into the area of the striatum richest in DA terminals failed to produce rotation or a significant change in TOH activity. We suggest that 5-HT neurons from the raphe nuclei exert a tonic inhibition on the nigrostriatal pathway at the level of the SN through direct synapses on DA neurons, whereas their neostriatal terminals have an indirect effect on DA terminals, perhaps via interaction with cholinergic and GABA-ergic neurons.

5,7-Dihydroxytryptamine↗

PubMed1981

Hippocampal serotonin re-uptake and nocturnal locomotor activity after microinjections of 5,7-DHT in the fornix-fimbria.

The role of the hippocampal 5-hydroxytryptamine (5-HT) terminals in the control of locomotor activity was investigated by lesioning 5-HT axons in the fimbria with 5,7-dihydroxytryptamine (5,7-DHT). Rats pretreated with desimipramine (10 mg/kg, i.p.) received microinjections of 5,7-DHT (0, 1, 3, 5 or 10 micrograms in 0.4 microliter ascorbic Ringer's solution) into the fornix-fimbria. On the fourteenth to twenty-first nights after operation, nocturnal locomotor activity was measured in photocell cages. Twenty-eight to thirty days after operation degeneration of 5-HT terminals was assessed by measuring in vitro [3H]5-HT re-uptake in slices of dorsal hippocampus, ventral hippocampus and the septum. Groups injected with 5,7-DHT showed hyperactivity in the night period and increased decrements of activity between tests, both of which were related to the dose of neurotoxin. A reduction of [3H]5-HT re-uptake was found in dorsal hippocampus which was related to the dose of 5,7-DHT), but ventral hippocampal and septal [3H]5-HT re-uptake were not systematically reduced. For each rat, levels of dorsal and ventral hippocampal [3H]5-HT re-uptake were negatively correlated with the mean nocturnal activity from the 7 nights of testing. Levels of dorsal, but not ventral hippocampal [3H]5-HT re-uptake were negatively correlated with the mean nightly decrement of activity. No correlations were found between septal [3H]5-HT and these activity measures. These results, indicate that the increase in nocturnal locomotor activity caused by generalized depletion of 5-HT in the brain may be due to disruption of hippocampal 5-HT terminals supplied by the fornix-fimbria.

5,7-Dihydroxytryptamine↗