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At least 199 records · Page 11Linked to original sources
PubMed1985

Potentiation of motoneurone excitability by combined administration of 5-HT agonist and TRH analogue.

Motoneurone field potentials have been recorded from the lumbar region of the spinal cord, to antidromic stimulation of a ventral root, in rats anaesthetised with urethane. Injection of the thyrotropin releasing hormone (TRH) analogue RX77368 (1mg/kg) plus the 5-hydroxytryptamine (5-HT) receptor agonist 5-methoxy-N, N-dimethyl-tryptamine (5MeODMT 0.4mg/kg) resulted in a potentiation of the increase in amplitude and duration of response, compared to when the drugs were given singly. These results are discussed in the context of possible interactions between 5-HT and TRH systems.

Animals↗
PubMed1982

Opposite effects of N,N-dimethyltryptamine (DMT) and 5-methoxy-n,n-dimethyltryptamine (5-MeODMT) on acoustic startle: spinal vs brain sites of action.

The present studies examined the role of the spinal cord and the brain in mediating the effects of the hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on the acoustic startle response in the rat. Systemic administration of these agents, which distributes to both the brain and spinal cord, produced opposite effects, as DMT depressed and 5-MeODMT increased acoustic startle. However, when administered directly into the lateral ventricle in the forebrain (intraventricular administration) 5-hydroxytryptamine (5-HT), DMT and 5-MeODMT all depressed acoustic startle, DMT and 5-MeODMT being about equipotent in this regard. In contrast, when administered directly into the spinal cord subarachnoid space (intrathecal administration), 5-HT and 5-MeODMT increased startle, whereas DMT was without effect. In another series of studies, the effects of systemically-administered DMT and 5-MeODMT on the "startle" elicited by electrical stimulation of the nucleus reticularis pontis caudalis (RPC) were determined. Since the RPC is the last nucleus of the primary startle circuit before the spinal cord, agents which act downstream from the RPC (i.e., in the lower brainstem and spinal cord) would be expected to alter RPC-elicited "startle," while agents which act upstream from the RPC would be without effect. Given systemically, 5-MeODMT markedly increased RPC-elicited "startle" while DMT was without effect. These data indicate that DMT and 5-MeODMT are equipotent in depressing startle through actions in the brain. In contrast, the difference in the effects of DMT and 5-MeODMT on acoustic startle is related to the spinal excitatory effects of 5-MeODMT which DMT does not possess. From the present results it is suggested that the relative potencies of DMT and 5-MeODMT in other behavioral measures may relate to the role of brain (equipotent) or spinal (5-MeODMT more potent than DMT) sites of action for the various behaviors.

Acoustic Stimulation↗
PubMed1985

Dissociation of head twitches and tremors during the study of interactions with 5-hydroxytryptophan in mice.

Intraperitoneal injection of 5-hydroxytryptophan and 5-methoxy-N,N-dimethyltryptamine is shown to provoke characteristic behaviors in mice that can be quantified. The two principal phenomena described here are head twitches and tremors. Tremors became more frequent when doses of the two substances studied were increased. Head twitches appeared at lower doses, but beyond a certain dose, they decreased and even disappeared. The effects on these movements of agents that modify serotonin function were then studied. The results pose problems of interpretation that are discussed.

Animals↗
PubMed1990

Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine.

In neonatal kittens, micturition is induced by a spinal somatovesical reflex pathway that is activated by the mother cat licking the perigenital region of the kitten. The somatovesical reflex pathway disappears about the time of weaning and is replaced by a vesicovesical reflex pathway that produces micturition via a supraspinal reflex pathway that is activated by distension of the urinary bladder. Furthermore, stimulation of the perigenital region in adult cats actually inhibits the supraspinal vesicovesical micturition reflex. Spinalization prompts the return of the somatovesical reflex, immediately in weaned kittens but over a course of days to weeks in adult cats. The purpose of the present experiments was to determine if the somatovesical reflex could be demonstrated acutely, and reversibly, in adult cats with an intact spinal cord via pharmacological suppression of the serotonergic system. The serotonergic system was suppressed by the intravenous administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a serotonin agonist that inhibits the firing of serotonergic neurons via activation of inhibitory somatodendritic autoreceptors. 5-MeODMT in low doses (20-50 micrograms/kg) abolished inhibition of the bladder produced by either light tactile stimulation of the perigenital region or by electrical stimulation of the pudendal nerve, which carries the afferent fibers from the perigenital region, in 9 of 10 adult cats. Furthermore, in 8 of the 10 cats, the bladder inhibition was reversed to an excitation of variable amplitudes in each cat. Higher doses of 5-MeODMT (100-1000 micrograms/kg) abolished spontaneous bladder activity but did not inhibit perigenital-induced bladder contractions in those 8 animals in which the drug unmasked the excitatory somatovesical reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗
PubMed1996

Role of hippocampal 5-HT1A receptors on elevated plus maze exploration after a single restraint experience.

Previous studies have shown that 2 h restraint stress induces deficits in open arm exploration of an elevated plus maze 24 h later. This effect was attenuated by a post-stress systemic injection of the 5-HT non-selective agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). To verify a possible involvement of hippocampal 5-HT1A receptors in this effect, rats were stereotaxically implanted with canulae in the dorsal hippocampus. Seven days later they received bilateral microinjections of 5-MeODMT (20 nmol/0.5 microliter) or saline. No difference was found on exploration of an elevated plus maze 24 h later. However, when treatments were performed immediately after 2 h of restraint stress, the drug was able to increase open arm exploration 24 h later. This effect was antagonized by a previous microinjection of (+)WAY-100135 (40 nmol/0.5 microliter), a selective 5-HT1A antagonist. The results suggest that hippocampal 5-HT1A receptors may attenuate stress behavioral consequences.

Animals↗
PubMed1993

Modulation of 5HT1A receptors in the hippocampus and the raphe area of rats treated with clonazepam.

1. Clonazepam is one of the most potent benzodiazepines known to decrease the activity of the central serotonergic systems. The acute and subchronic administration of clonazepam reduced serotonin (5HT) turnover rate in the hippocampus of the rat, as determined by the ratio of the monoamine and its metabolite, 5-hydroxyindoleacetic acid. 2. The modulation of 5HT binding sites and 5HT1A receptors by the administration of clonazepam for various periods of time were studied in the hippocampus and the raphe area by experiments with radioligands. 3. The density of [3H]5HT recognition sites increased in the hippocampus of clonazepam-treated rats in a dose- and time-dependent manner. This increase was impaired by the simultaneous administration of the 5HT agonist 5-methoxy-N,N-dimethyltryptamine. The affinity of this binding did not significantly change. This observation might indicate an increase in some of the 5HT receptors or an increase of the uptake site. 4. The binding parameters for [3H]DPAT, Bmax and Kd, decreased in the hippocampus but not in the raphe area of clonazepam-treated rats. It seems that the presynaptic reduction in 5HT function, resulting in the decrease of its availability at the synaptic space, modifies the corresponding 5HT recognition sites. 5. These changes could be related to the anxyolitic activity or the withdrawal symptoms of benzodiazepines.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Serotonergic involvement in the regulation of prolactin and vasoactive intestinal peptide mRNA expression in the rat anterior pituitary.

These studies examined the contribution of serotonin (5-HT) to the control of prolactin (PRL) and vasoactive intestinal peptide (VIP) messenger RNA expression in rat anterior pituitary. Daily injection of rats with the biosynthetic precursor to serotonin, 5-hydroxytryptophan (5-HTP; 25 mg/kg, q.i.d.), resulted on day 5 in a 50% increase in the expression of PRL mRNA in the pituitary while at the same time reducing the levels of both the 1.0 and 1.7 kb VIP mRNA transcripts. Co-treatment of rats with 5-HTP plus the catecholamine biosynthesis inhibitor, alpha-methyl-tyrosine (alpha-MT; 150 mg/kg, q.d. x 2 days), or the dopamine receptor antagonist haloperidol (1.25 mg/kg, b.i.d. x 5 days), resulted in increases in pituitary PRL message levels that were greater than those observed with either anti-dopaminergic agent alone. In contrast, 5-HTP was unable to reverse the inhibition of PRL mRNA expression caused by treatment with the dopamine receptor agonist bromocriptine (2.5 mg/kg, b.i.d. x 5 days). Neither alpha-MT, haloperidol nor bromocriptine had a significant effect on pituitary VIP mRNA expression. Administration of the direct-acting 5-HT receptor agonist quipazine (5 mg/kg, b.i.d.) for 14 consecutive days caused a significant increase in pituitary PRL mRNA levels on day 1 and reached a plateau of 90% above control levels on days 7 and 14. VIP mRNA levels rose significantly on day 1 of quipazine treatment but thereafter fell to a minimum of 22% (1.0 kb) and 52% (1.7 kb) of control by day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1980

Nociception is enhanced after low doses and reduced after high doses of the serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine.

The effects on pain sensitivity of intracerebroventricular injections of 5-methoxy-N,N-dimethyltryptamine were tested by the tail-flick method. Following administration of 1.6, 3.1, 6.3, 12.5 and 25 micrograms (n = 8 for each dose), tail-flick latencies were reduced by 13-24%. Fifty and 100 micrograms caused a biphasic response (hyperalgesia followed by analgesia), whereas 400 micrograms increased mean latencies by 28-39%. The hyperalgesia observed after low doses was most likely due to reduced activity in descending serotonergic neurons following presynaptic stimulation. Higher doses caused analgesia, probably by stimulating spinal postsynaptic serotonergic receptors as well.

Animals↗
PubMed1982

Serotonin involvement in aversive conditioning: reversal of the fear retention deficit by long-term p-chloroamphetamine but not p-chlorophenylalanine.

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a serotonin (5-HT) agonist, fenfluramine and p-chloroamphetamine (PCA), which are 5-HT releasers, produce deficits in fear retention as indicated by a notable lack of the immobility resulting from inescapable shocks. Depletion of central 5-HT neurones after long-term PCA treatment (2 X 10 mg/kg) completely blocked the retention impairment resulting from acute PCA (2.5 mg/kg) and fenfluramine (5 mg/kg), and partially blocked the deficit produced by 5-MeO-DMT (4 mg/kg). 5-HT depletion after p-chlorophenylalanine (PCPA) treatment (200, 100, 100 mg/kg, 72, 48 and 24 h before) did not do so; this is in agreement with other findings which suggest the involvement of different 5-HT stores in the action of PCA and PCPA. These data further underline the importance of the ascending 5-HT pathway in aversive conditioning in the rat.

Amphetamines↗
PubMed1982

Nociception is enhanced by the intrathecal injection of 5-methoxy-N,N-dimethyltryptamine in the rat.

The effect of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) at the spinal cord level on nociceptive reflexes was tested using the tail-flick assay in rats. 5-MeODMT was injected directly into the spinal subarachnoid space of conscious rats via a permanently indwelling intrathecal cannula. Administration of 100 micrograms/rat of 5-MeODMT into the thoracic region, using a 4 cm long cannula, reduced the average percent of control reaction time by 14%. The injection of the same dose of 5-MeODMT into the lumbosacral region, via an 8.6 cm long cannula, decreased the average percent of control reaction time by 25%. The ability of 5-MeODMT to mimic the facilitatory (hyperalgesic) effect on nociception of similar doses of tryptamine, in contrast to the antinociceptive (analgesic) effect of serotonin, suggests an interaction of 5-MeODMT with tryptaminergic rather than serotonergic receptors in the spinal cord.

Animals↗
PubMed1987

Phencyclidine-induced head-twitch responses as 5-HT2 receptor-mediated behavior in rats.

This study was designed to assess whether phencyclidine (PCP)-induced head-twitch was antagonized by ritanserin, a selective serotonin (5-HT2) receptor antagonist, in mice and rats to confirm the involvement of 5-hydroxytryptamine (5-HT) neurons in PCP actions in comparison with 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced behavior. PCP (7.5, 10 and 12.5 mg/kg, i.p.)-induced head-twitch was completely antagonized by ritanserin (1 mg/kg, s.c.) in mice and rats, and 5-MeODMT (2 and 4 mg/kg, i.p.)-induced head-twitch was also completely antagonized by ritanserin in mice. PCP and 5-MeODMT induced head-weaving in mice after ritanserin treatment, but this did not occur in rats. In rats, 5-MeODMT failed to induce head-twitch. These results suggest that PCP-induced head-twitch response in rats is developed via 5-HT2 receptors and it is a useful 5-HT2 receptor model, while 5-MeODMT-induced head-weaving in rats is developed via 5-HT1 receptors and is a useful 5-HT1 receptor model.

Animals↗
PubMed1988

Intrathecal substance P modulates the depressant effect of 5-methoxy-N,N-dimethyltryptamine on a reflex response to radiant heat in mice.

The effect of intrathecal (i.th.) substance P (SP) on antinociception elicited by the serotonin (5-HT) receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) was investigated in mice by means of the tail-flick method. Substance P (0.07, 0.7 or 7 micrograms) induced a behavioral syndrome for 1-2 min, but had no apparent toxic or neurologic effects and did not alter the tail-flick response to noxious radiant heat 30 min after injection. The depressant effect of 5-MeODMT (3 mg/kg) on tail-flick responses was, however, markedly attenuated when administered 30 min after SP. The tail skin temperatures of vehicle- and SP-injected mice were nearly identical 30 min after i.th. injection as well as after administration of 5-MeODMT. The results indicate a functional interaction between SP and 5-HT in spinal nociceptive processes, and it is suggested that i.th. SP modulates the function of 5-HT receptors.

Animals↗
PubMed1989

Serotonergic dorsal raphe neurons: changes in spontaneous neuronal activity and responsiveness to 5-MeODMT following long-term amphetamine administration.

Single-unit activity, characteristic of serotonergic neurons, was recorded in the dorsal raphe nucleus of urethane-anesthetized rats pretreated twice daily with saline or with 10.0 mg/kg D-amphetamine for 6 days. Compared to controls, amphetamine-pretreated animals showed a trend toward increased spontaneous firing rate and decreased responsiveness to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a serotonergic autoreceptor agonist. The most pronounced effect of amphetamine pretreatment, however, was a highly significant correlation between spontaneous neuronal activity, measured as either firing rate or interspike interval, and the 5-MeODMT response. Faster firing cells required predictably higher doses of 5-MeODMT to produce an inhibition. No such relationship was observed in control animals. Taken together, these results suggest that repeated administration of relatively high doses of amphetamine produces complex changes in the dorsal raphe including a shift in the sensitivity of serotonergic autoreceptors.

Action Potentials↗
PubMed1992

Behavioral and electroencephalographic effects of a serotonin receptor agonist (5-methoxy-N,N-dimethyltryptamine) in a feline model of photosensitive epilepsy.

The effects of a serotonin (5-HT) receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), on epileptic photosensitivity were studied in the lateral geniculate-kindled cat. 5-MeODMT at 4 mg/kg significantly suppressed photically induced myoclonus, but not paroxysmal EEG activity, at 0.5-1 h after injection. This antiepileptic effect was seen in association with the appearance of behavioral signs similar to those seen in the 5-HT syndrome. The present data provide further evidence that 5-HT plays an important role in photosensitive epilepsy, and suggest that the inhibitory effect of 5-MeODMT on photosensitivity results from its agonist action at 5-HT1 receptors.

Animals↗
PubMed1988

Acute and chronic treatment with selective serotonin uptake inhibitors in mice: effects on nociceptive sensitivity and response to 5-methoxy-N,N-dimethyltryptamine.

The tail-flick and increasing temperature hot-plate tests were employed to study the effects of acute or chronic treatment with zimelidine, alaproclate or chlorimipramine on nociception and response to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in mice. A single dose of the serotonin (5-HT) uptake inhibitors produced antinociception in the hot-plate test but not in the tail-flick test. After chronic administration, reduced tail-flick latencies were demonstrated 24, 48, 72 and 144 h after withdrawal of zimelidine treatment, 48 h after withdrawal of alaproclate and 48 and 96 h after withdrawal of chlorimipramine treatment. The hot-plate response temperatures were slightly lowered after chronic zimelidine treatment but not after treatment with alaproclate or chlorimipramine. The response to 5-MeODMT was not altered by a single dose of the 5-HT uptake inhibitors, however, after withdrawal of chronic treatment this response was increased in the tail-flick test but not in the hot-plate test. It was concluded that acute and chronic treatment with 5-HT uptake inhibitors modulate nociception differently, and that chronic treatment induces supersensitivity of spinal postsynaptic 5-HT receptors. Different modulation of different 5-HT receptor subpopulations by these compounds may possibly contribute to the test-dependent results.

Alanine↗
PubMed1993

The serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine facilitates noradrenaline release from rat spinal cord slices and inhibits monoamine oxidase activity.

1. The influences of the purported serotonergic agonist 5-methoxy-N,N-dimethyltryptamine (MeODMT) on noradrenaline release and metabolism were investigated in a rat spinal cord release model and a monoamine oxidase (MAO) assay. 2. MeODMT inhibited the basal outflow of tritium from rat spinal cord slices preincubated with [3H]noradrenaline and enhanced the electrically-evoked overflow. 3. Effects on basal outflow were not observed, when monoamine oxidase (MAO) was inhibited by pargyline. Effects on the evoked overflow were not observed in the presence of metitepine or phentolamine. 4. Preferential inhibition by MeODMT of MAO A-type enzyme activity was found in a direct assay. 5. The results provide evidence for two different effects by which MeODMT reinforces noradrenergic neurotransmission in the rat spinal cord: facilitation of stimulation-evoked noradrenaline release and inhibition of noradrenaline metabolism by MAO inhibition.

Animals↗
PubMed1984

The distribution of serotonin binding sites in the hippocampal region of the rat brain. An autoradiographic study.

The distribution of serotonin binding sites was studied in the rat hippocampal region by using contact-film autoradiography after in vitro incubations of brain sections with 5-[3H]hydroxytryptamine, [3H]spiperone, and [3H]ketanserin, respectively. Biochemical studies of the 5-[3H]hydroxytryptamine binding to sections cut through the hippocampal region showed that at saturating concentrations of 5-[3H]hydroxytryptamine (2-2.5 nM) the specific binding was at least 50% of the total. The 5-[3H]hydroxytryptamine binding sites were found to be heterogeneously distributed within the hippocampal region with the highest densities present in the following parts: layers I and II and layers IV through VI of the entorhinal area, the radial layer of the subiculum and subfield CA1 of the Ammon's horn and the molecular layer of the area dentata. Moderate to low densities of binding was observed in layer III of the entorhinal area, the pre- and parasubiculum, the stratum pyramidale of the Ammon's horn, and the granular cell layer of the area dentata. Removal of the 5-hydroxytryptamine nerve terminals by systemic injections of the 5-hydroxytryptamine neurotoxin parachloroamphetamine resulted in no detectable reductions of 5-[3H]hydroxytryptamine binding in any brain region. Lesions of hippocampal cell bodies by intrahippocampal injections of ibotenic acid prevented the binding of 5-[3H]hydroxytryptamine within the area of the cell loss. Comparisons between the distribution of 5-hydroxytryptamine immunoreactive nerve terminals and the 5-[3H]hydroxytryptamine binding sites showed that in some areas of sparse 5-hydroxytryptamine innervation the 5-[3H]hydroxytryptamine binding was close to background (e.g. the pyramidal cell layer, the stratum lucidum) whereas in areas with little 5-[3H]hydroxytryptamine binding (e.g. layer III of the lateral entorhinal area, the presubiculum) a very dense 5-hydroxytryptamine innervation was found. The hippocampal 5-[3H]hydroxytryptamine binding was displaced neither by ketanserin (1 microM) nor by spiperone (1 microM), two drugs that bind to cortical 5-hydroxytryptamine2 receptors in the rat brain. Furthermore, the pattern of hippocampal [3H]spiperone binding differed considerably from that of 5-[3H]hydroxytryptamine. The [3H]ketanserin binding in the hippocampal region did not exceed background levels, except in the hilus of area dentata in the ventral hippocampus and entorhinal layer VI at the same level, where moderate binding was found.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗