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PubMed2001

A role for serotonin in lipopolysaccharide-induced anorexia in rats.

Rats consistently reduce their food intake following injection of bacterial lipopolysaccharides (LPS). Because LPS increases CNS serotonin (5-HT) turnover, and because increases in CNS 5-HT turnover are associated with a decrease in food intake, we conducted a series of studies to examine 5-HT's potential role in LPS-induced anorexia. Chronic CNS 5-HT depletion by cisterna magna (CM) administration of 5,7-dihydroxytryptamine (5,7-DHT) failed to attenuate LPS-induced (100 microg/kg, ip) anorexia. In subsequent experiments, LPS was injected at lights out (hour 0) and [8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT)] or N-CBZ-[(8beta)-1,6-dimethylergolin-8-yl]methylamine (metergoline) was injected at hour 5 - the time when LPS-treated rats become anorectic. Food intake was measured during the subsequent 2 h. In LPS-treated rats, 8-OH-DPAT (62.5, 125, or 250 microg/kg, sc) injection increased food intake. In a 2 x 2 factorial arrangement of LPS and 8-OH-DPAT, 125 microg/kg 8-OH-DPAT increased food intake significantly more in LPS-treated rats than in non-LPS-treated rats (significant LPS x 8-OH-DPAT interaction). In LPS-treated rats, 1 and 5 mg/kg metergoline significantly enhanced food intake. However, in a 2 x 2 arrangement of LPS and metergoline, 1 mg/kg metergoline failed to increase food intake in LPS and non-LPS-treated rats in two separate trials. The ability of the 5-HT(1A) receptor agonist 8-OH-DPAT to attenuate LPS-induced anorexia in rats supports a role of 5-HT in LPS-induced anorexia.

5,7-Dihydroxytryptamine↗
PubMed1984

Effects of serotonergic and cholinergic antagonists on suckling behavior of neonatal, infant, and weanling rat pups.

In Experiment 1, Sprague-Dawley rat pups at postnatal days 3-4, 7-8, 10-11, 15-16, and 23-24 were tested for suckling behavior on their anesthesized multiparous dams following administration of metergoline or scopolamine. The serotonergic antagonist, metergoline, inhibited suckling in 3- to 4- and 7- to 8-day-old rat pups, but was not found to influence suckling in older pups. Scopolamine, a cholinergic antagonist, reduced suckling primarily in 3- to 4-day-old pups. In Experiment 2, parity of the maternal female was manipulated to assess whether this variable would influence suckling behavior and the effects of metergoline on suckling of weanlings. Baseline levels of suckling were reduced in 23- to 24-day-old pups of primiparous dams when compared with multiparous-derived offspring. Administration of metergoline increased the amount of time that these primiparous-derived pups spent attached to nipples, but did not influence suckling of offspring of multiparous dams, perhaps as a result of a ceiling effect on suckling behavior in these animals.

Acetylcholine↗
PubMed1989

The role of tail skin temperature in the facilitation of the tail-flick reflex after spinal transection or interference with descending serotonergic neurotransmission.

We examined in mice whether tail skin temperatures and tail-flick reflexes were changed after spinal transection or intrathecal (i.th.) injection of the serotonin (5-HT) neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) or the 5-HT receptor antagonist metergoline. Transection of the spinal cord reduced tail-flick latency (the time needed to evoke the tail-flick reflex by radiant heat) and increased tail skin temperature 15-21 days after surgery. Analysis of covariance showed that the effect of tail skin temperature on tail-flick latency was far more pronounced than the effect of spinal transection. Intrathecal injection of 5,6-DHT (5 or 10 micrograms mouse-1), which extensively reduced the spinal levels of 5-HT, reduced tail-flick latency and increased tail skin temperature 1-5 days after treatment. Similarly, tail-flick latency was shortened and tail skin temperature elevated 15 min after i.th. injection of metergoline (0.5 micrograms mouse-1). Analysis of covariance showed no significant effect of i.th. 5,6-DHT or i.th. metergoline on tail-flick latency. Tail skin temperature, on the other hand, had a highly significant effect on tail-flick latency. The results show that the facilitation of the tail-flick reflex in spinally transected mice and mice injected i.th. with 5,6-DHT or metergoline is mainly caused by increased tail skin temperature. The data do not indicate that descending 5-HT pathways tonically inhibit the tail-flick reflex.

5,6-Dihydroxytryptamine↗
PubMed1990

5-HT1-, but not 5-HT2-serotonergic, M1-, M2-muscarinic cholinergic or dopaminergic receptors mediate the ACTH/cortisol response to metoclopramide in man.

The possible mediation of dopaminergic, muscarinic cholinergic and/or serotonergic receptors in the response of ACTH/cortisol to metoclopramide (MCP) was evaluated in 27 normal men. All subjects were tested with MCP (10 mg in an intravenous bolus plus placebo or saline, NaCl 0.9%, control test). For the other tests (experimental tests), the men were divided into three groups of 9 subjects each. One group was tested with MCP in the presence of the dopaminergic agonist bromocriptine (5 mg p.o. 3 h before MCP), another group was tested with MCP plus the M1- and M2-muscarinic-cholinergic antagonist atropine (1.2 mg in an intravenous bolus, just before MCP) or the M1-muscarinic receptor blocker pirenzepine (40 mg in an intravenous bolus 10 min before MCP). The third group was tested with MCP after treatment with the selective 5-HT1-serotonergic receptor blocker metergoline (10 mg/day p.o. in 5 divided doses for 4 days before MCP) or the 5-HT2-serotonergic receptor antagonist ketanserin (10 mg as a slow 3-min intravenous injection, 5 min before MCP). ACTH and cortisol rose by 45 and 55%, respectively, in response to MCP. The basal levels of ACTH and cortisol were not modified by bromocriptine, atropine, pirenzepine, metergoline or ketanserin treatment. Both ACTH and cortisol responses to MCP did not change significantly after bromocriptine, atropine, pirenzepine or ketanserin administration, whereas they were completely abolished by pretreatment with metergoline. Additional experiments were performed in order to evaluate whether the effect of metergoline on the ACTH/cortisol response to MCP depends on the amount of the serotonergic antagonist (dose-response study).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1975

Inhibition of ACTH response to oral and intravenous metyrapone by antiserotoninergic treatment in man.

Plasma ACTH levels after oral and iv metyrapone administration were studied in 7 and 5 healthy women respectively both under basal conditions and after a 4-day treatment with metergoline, a specific antiserotoninergic agent. In 3 additional women, the effects of methysergide, another antiserotoninergic drug, on the plasma ACTH rise induced by oral metyrapone, were evaluated. A significant lowering of the plasma ACTH levels attained after either oral or iv metyrapone was observed following metergoline administration: 149+/-64.3 vs 239+/-49.1 pg/ml (mean peak values), P less than 0.05 in the oral test and 331+/-19.7 vs 221+/-19.5 pg/ml, P less than 0.02 in the iv test. The fall of plasma cortisol caused by metyrapone was comparable before and after the antiserotoninergic treatment. An interference of metergoline in the ACTH radioimmunoassay was also excluded. After metergoline administration, a slight reduction in the baseline plasma ACTH values was noted: 79+/-7.7 vs 67+/-7.7 pg/ml (NS). A decrease, however not statistically significant, of the metyrapone-induced plasma ACTH elevation occured after methysergide administration: 421+/-150.7 vs 344+/-135.1 pg/ml. These results can be interpreted as indicating that antiserotoninergic treatment caused an inhibition of hypophysial ACTH release in response to metyrapone. Caution is recommended, however, before concluding, on the basis of these findings, that serotonin as such plays a physiological stimulating role on ACTH secretion.

Administration, Oral↗
PubMed1979

[Effect of pretreatment with metoclopramide on plasma prolactin response to methergoline].

The Authors examined 20 voluntary women without endocrine diseases. The women took 4 mg of metergoline orally and 30-60-90-120-180-240 minutes after the medicament was given the serum prolactin levels were tested. After 3 weeks, 14 among 20 subjects repeated the test assuming during the 3 days before 50 mg of metoclopramide orally once a day. The Authors found a remarkable decline of prolactin serum levels after metergoline administration in all subjects. After metoclopramide administration prolactin serum levels increased meaningly. Metergoline administration gave again considerable fall of prolactin serum levels in the 14 subjects. From the data the Authors affirm that metergoline inhibits prolactin secretion with an antiserotonine action

Adult↗
PubMed2004

Study of the behavioural responses related to the potential addictive properties of MDMA in mice.

We investigated several behavioural responses induced by repeated administration of MDMA in mice that could be related to its potential abuse liability. Mice treated with MDMA at the dose of 10 mg/kg displayed a significant conditioned place preference with respect to saline treated controls, while lower doses (0.3, 1.0, 3.3 mg/kg) had no effect. The development of physical dependence was also investigated. Mice were treated with MDMA (10 mg/kg) twice daily for 5 days. On day 6, following a single administration of MDMA mice received the following monoaminergic antagonists: metergoline (0.1 and 1 mg/kg), ritanserin (0.25 and 1 mg/kg), timolol (2 and 10 mg/kg), prazosin (0.25 and 1 mg/kg), SCH 23390 (0.05 and 0.25 mg/kg), raclopride (0.1 and 0.5 mg/kg) or vehicle, and several somatic manifestations of withdrawal were evaluated for 45 min. Metergoline induced paw tremor, face rubbing, as well as an increase in locomotor activity in mice chronically treated with MDMA. Ritanserin, and timolol induced only paw tremor, while SCH 23390 and raclopride did not produce any somatic manifestation indicative of abstinence. The possible modification of the rewarding properties of MDMA (10 mg/kg) by the monoaminergic antagonists producing the most relevant somatic signs of withdrawal namely, metergoline (0.1 and 1 mg/kg) and timolol (2 and 10 mg/kg) were tested in the conditioned place preference paradigm. Results showed that metergoline did not significantly modify the rewarding properties of MDMA, whereas only the highest dose of timolol was able to decrease MDMA reward. No signs of dopaminergic neurotoxicity were observed following chronic treatment with MDMA as revealed by [(3)H] mazindol binding. The possible motivational and affective components of the withdrawal syndrome were assessed in the suppression of operant responding for food, the conditioned place aversion, and the lit/dark paradigms. Results showed that the somatic symptoms observed were not accompanied by any aversive/dysphoric or anxiogenic-like behaviours. These results reveal the rewarding properties of MDMA in mice, and suggest that chronic MDMA administration does not induce classical manifestations of physical dependence in mice.

Animals↗
PubMed1981

Inhibition of neurotransmitter receptor binding by ergot derivatives.

Bromocriptine, lergotrile, lisuride, metergoline, and the Sandoz ergot derivatives 25-397, 29-712, and 29-717 have been tested for their ability to inhibit the synaptic receptor binding of spiroperidol, 5-hydroxytryptamine (5-HT), d-lysergic acid diethylamide (LSD), quinuclidinyl benzilate (QNB), WB.4101, and gamma-aminobutyric acid (GABA). Only GABA binding was not affected, and QNB binding was decreased only by lergotrile and metergoline at high concentrations. The most potent inhibitors of the other ligands were bromocriptine and lisuride for spiroperidol (1-2 nMM), metergoline for 5-HT (29 nM), lisuride for LSD (15 nM), and lergotrile for WB.4101 (17 nM). The direct receptor effects of the ergot derivatives in vitro may contribute to understanding their in vivo effects on behavior and in predicting their therapeutic potential in neurological and neuroendocrine disorders.

Adrenergic alpha-Antagonists↗
PubMed1991

Analysis of neurotransmitter receptors mediating changes in LH release induced by electrical stimulation of the dorsal raphe nucleus in the rat.

We report studies of neurotransmitter and receptor species mediating the inhibition of LH release in ovariectomized (OVX) rats and stimulation in OVX estrogen-primed rats induced by electrical stimulation of the dorsal raphe nucleus (DRN). Attempts were made to block effects of stimulation of the DRN in groups of four to nine ovariectomized rats with or without priming with estradiol benzoate (EB) by pretreatment with the 5HT receptor antagonists ketanserin, methysergide, or metergoline; the alpha-adrenergic antagonist phenoxybenzamine; or the opiate antagonist naltrexone. Blood samples were collected via jugular cannulae from the unanesthetized rats at 10-min intervals before and during electrical stimulation of the DRN, and assayed by double antibody radioimmunoassay for LH. To test the effect of stimulation, data from animals in each treatment group were subjected to analysis of variance to obtain the contrast matrix including prestimulation and stimulation time points of interest. The contrast matrix was then used to construct an F ratio and thereby to evaluate the level of significance. In unprimed OVX rats the sustained decrease in plasma LH concentration during stimulation was prevented in rats pretreated with ketanserin or phenoxybenzamine. Methysergide pretreatment delayed the inhibitory effect of DRN electrical stimulation for 30 min, whereas metergoline and naltrexone were ineffective. In EB-primed animals the increase in plasma LH observed during stimulation was prevented in rats pretreated with metergoline, and reversed in those receiving naltrexone. Ketanserin limited the duration of the increase to 10 min, while phenoxybenzamine and methysergide had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Evidence that serotonin receptors are involved in the anticonvulsant effect of yohimbine in mice.

The threshold of seizures induced by electroconvulsive shock (ECS) was determined in mice and the effects of alpha 2-adrenoceptor antagonists (yohimbine, rauwolscine, idazoxan), alpha 2-adrenoceptor agonists (clonidine, B-HT 920), serotonin antagonists (methysergide, metergoline) and a serotonin agonist (quipazine) were studied. The interaction of yohimbine with clonidine, methysergide, metergoline and quipazine was also examined. It was found that yohimbine and rauwolscine elevated the seizure threshold, while idazoxan was ineffective. Clonidine and B-HT 920 were also ineffective, but quipazine elevated the seizure threshold. Methysergide and metergoline did not change the seizure threshold alone, but both of them antagonized the anticonvulsant effect of yohimbine. Clonidine failed to antagonize yohimbine's effects. Quipazine potentiated yohimbine's action. These results suggest that, in mice, the protective effect of yohimbine against ECS-induced seizures may be mediated via serotonin receptors and not via alpha 2-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1983

Serotonergic excitation of sympathetic preganglionic neurons: a microiontophoretic study.

The effects of microiontophoretically applied serotonin on the extracellularly recorded discharges of sympathetic preganglionic neurons (SPNs) were studied in anesthetized cats. Thoracic SPNs were identified on the basis of constancy of antidromic activation and collision. Low ejecting currents of serotonin (5-30 nA) invariably excited spontaneously active SPNs. Serotonin also excited the vast majority of quiescent SPNs, as well as neurons brought to discharge threshold by the excitatory amino acid L-glutamate. A population of SPNs was identified which was insensitive to the excitatory effects of both serotonin and L-glutamate. Iontophoretic or intravenous administration of the putative serotonin antagonists methysergide and metergoline blocked the excitatory effects of serotonin on SPNs. The blockade of the serotonin-induced excitation was not associated with a local anesthetic action of methysergide or metergoline. Methysergide and metergoline also reduced the firing rate of SPNs in intact but not in spinal animals. These data provide strong evidence to support the contention that serotonergic neurons provide a tonic excitatory input to SPNs.

Animals↗
PubMed1979

Interaction of sulfpride and ergot derivatives on rat brain DOPAC concentration and prolactin secretion in vivo.

Sulpiride, which differs from classical neuroleptics by not producing major extrapyramidal side effects, is a potent antiemetic agent and stimulates prolactin secretion in both laboratory animals and man. In parallel it increases dopamine synthesis in both striatum and nucleus accumbens. Bromocriptine and metergoline are two effective agents in suppressing prolactin release and postulated to stimulate dopamine receptors. The interactions of these two ergot derivatives with sulpiride have been investigated on prolactin release and on striatal and limbic DOPAC accumulation. Bromocriptine at all doses tested was able to suppress the increased in vivo prolactin secretion observed after sulpiride administration. Metergoline antagonized the sulpiride-induced prolactin increase only at low doses; on the contrary higher doses potentiated it. High concentrations of bromocriptine suppressed the sulpiride-induced increased of DOPAC levels in striatum and n. accumbens, while metergoline potentiated the sulpiride-induced accumulation of brain DOPAC.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Pharmacological characterization of serotonin receptors in the facial motor nucleus: a microiontophoretic study.

The effects of 'peripheral' serotonin (5-HT) antagonists on the facilitation of facial motoneuron excitation by 5-HT were investigated in the present study. Microiontophoretic application (5--10 aA) or intravenous administration of methysergide (0.5--1.0 mg/kg), cyproheptadine (0.5--1.0 mg/kg), cinanserin (0.5--1.0 mg/kg), or metergoline (50--100 micrograms/kg) antagonized the facilitating effect of 5-HT but not that of norepinephrine (NE) on facial motoneurons. Blockade developed within 1--2 min of the intravenous administration of methysergide, cyproheptadine and cinanserin and continued up to 30 min. The antagonism produced by intravenous metergoline took 8--15 min to develop and lasted for at least 6 h. Chronic administration of metergoline resulted in supersensitivity to 5-HT and NE in the facial nucleus. The putative 5-HT antagonists chlorpromazine, propranolol, and methiothepin failed to block the facilitating effect of 5-HT; however, methiothepin did block NE. The results are discussed in relation to a two-component model of the 5-HT mediated motor syndrome consisting of : (1) patterned excitatory inputs to motor nuclei; (2) 5-HT facilitation of these excitatory inputs. The 'peripheral' 5-HT antagonists appear to directly block the latter component.

Animals↗
PubMed1989

Evidence that central 5-HT2 receptors do not play an important role in the anorectic activity of D-fenfluramine in the rat.

To gain information on the role of central 5-HT2 receptors in the reduction of food intake caused by D-fenfluramine in rats, different intraperitoneal doses of metergoline, a non-selective 5-HT receptor antagonist and ritanserin, a selective 5-HT2 receptor antagonist, were compared for their ability (a) to antagonize the anorectic effect of D-fenfluramine; (b) to occupy central 5-HT2 receptors in vivo (measured by the binding of [3H]spiperone in the frontal cortex) and (c) to affect the concentrations of D-fenfluramine and its active metabolite, D-norfenfluramine in brain. Metergoline dose-dependently reduced the effect of D-fenfluramine (2.5 mg/kg i.p.) on food intake, with complete antagonism at 1 mg/kg, a dose which occupies about 50% of cortical 5-HT2 receptors. Ritanserin, at a dose (0.5 mg/kg) causing 50% occupation of 5-HT2 receptors, had no effect on anorexia induced by D-fenfluramine and only partially prevented it at doses which caused maximum occupation of 5-HT2 receptors (1-2 mg/kg). Unlike 1 mg/kg metergoline, 1 mg/kg ritanserin significantly reduced the concentrations of D-norfenfluramine in the frontal cortex and hypothalamus of rats 30 min after injection of D-fenfluramine. The results suggest that 5-HT receptors, other than 5-HT2, possibly 5-HT1B, are involved in the anorectic effect of D-fenfluramine in food-deprived rats.

Animals↗
PubMed1992

Are 5-HT receptors or beta-adrenoceptors involved in idazoxan-induced food and water intake?

Idazoxan (10 mg/kg, i.p.) produces an unexpected increase in food intake in freely-feeding rats which has been linked to its high affinity for non-adrenoceptor idazoxan binding sites. In this study, a dose-related antagonism of idazoxan-induced food intake by the beta-adrenoceptor antagonist (-)-propranolol (5-20 mg/kg, i.p.), which also blocks 5-HT1 (5-hydroxytryptamine1) receptors has been demonstrated. (+)-Propranolol (10, 20 mg/kg, i.p.) did not attenuate idazoxan-induced feeding. (-)-Propranolol (10 mg/kg, i.p.) but not the (+)-enantiomer (10 mg/kg, i.p.) also significantly inhibited the food intake, induced by the 5-HT1A agonist 8-OH-DPAT (0.25 mg/kg, i.p.). Idazoxan-induced feeding was not altered by the selective beta-adrenoceptor antagonists betaxolol (beta 1; 5 mg/kg, i.p.) and ICI 118,551 (beta 2; 5 mg/kg, i.p.) but was potentiated by the 5-HT receptor antagonist metergoline (5 mg/kg, i.p.). The anomalous findings with metergoline may reflect its action at different sub-types of 5-HT receptor. The water intake induced by idazoxan and the peripherally-active alpha 2-adrenoceptor antagonist L-659,066 was also blocked in a stereoselective manner by propranolol (10 mg/kg) but not significantly by either metergoline (5 mg/kg, i.p.), the beta 1-adrenoceptor antagonist betaxolol (5 mg/kg, i.p.) nor by the beta 2-adrenoceptor antagonist ICI 118,551 (5 mg/kg, i.p.). These results suggest that the food intake induced by idazoxan (and perhaps mediated by non-adrenoceptor idazoxan binding sites) may involve the 5-HT system, although further studies, using antagonists acting selectively at the different sub-types of 5-HT receptor, are required to confirm this.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Serotoninergic modulation of sodium appetite in the rat.

There are two mechanisms leading to an enhancement of salt intake: one is induced by a sodium deficit and the other is need-free. The serotonin involvement in need-induced and/or need-free sodium appetite is interesting to consider because related drugs are already used against another cardiovascular risk factor, obesity. The effect of dexfenfluramine (1.5 or 3 mg/kg), an anorectic drug enhancing 5-HT transmission, and of metergoline (2 or 4 mg/kg), a 5-HT antagonist, was assessed in need-induced (depletion-induced), subsequent need-free, and spontaneous sodium appetite. Dexfenfluramine (3 mg/kg) decreased by 75% to 90% the depletion-induced intake of an aversive 3% NaCl solution, as well as the spontaneous intake of a less aversive 1.8% NaCl solution. Water intake was not diminished under these conditions. Metergoline significantly increased salt intake in need-free conditions in rats with either a history of three previous depletions or not. These results confirm the involvement of serotonin in sodium appetite and extend this involvement to both need-induced (natriorexis) and need-free (natriophilia) conditions. The metergoline experiments also suggest that 5-HT exerts a tonic inhibition on salt intake.

Animals↗
PubMed1984

Effects of d-amphetamine and d-fenfluramine on performance of rats in a food maze.

d-Amphetamine and d-fenfluramine caused different patterns of disruption in a learned maze performance reinforced with food. A 0.8 mg/kg dose of amphetamine increased correct and incorrect (errors) alley entrances as well as earned reinforcers consumed. Larger doses (1.6-3.2 mg/kg) decreased correct responses, increased errors, and resulted in earned reinforcers not being consumed. Metergoline pretreatment did not reverse these deficits. d-Fenfluramine (1.5 and 3.0 mg/kg) reduced correct responses dose- relatedly with a slight increase in errors after the larger dose; all earned reinforcers were consumed. Pretreatment with metergoline reversed the deficit in correct responses but not the errors. Combinations of d-amphetamine and d-fenfluramine produced greater deficits than each drug separately, with fewer correct responses and an increase in reinforcers earned but not consumed. Metergoline pretreatment before the combination did not reverse these effects but increased alley entrances scored as errors. The results indicate that the d-fenfluramine but not the d-amphetamine deficit relates to a 5-hydroxytryptamine (5-HT) mechanism. Furthermore, the enhanced effect of the combination appears to relate to drug interactions not dependent upon a 5-HT component.

Animals↗
PubMed1982

Neurotransmitter basis of the behavioral effects of hallucinogens.

Indole and phenethylamine-type hallucinogenic drugs were studied in an FR-40 operant behavioral procedure programmed to quantify "pausing,"-a behavioral disruption somewhat specific to hallucinatory drug effects. LSD, DOM, DMT and mescaline showed a potency ratio to produce pausing that is well correlated with the hallucinatory potencies of these agents in man. Furthermore, combinations of the hallucinogens interact with potentiation to cause FR-40 pausing, whereas a variety of non-hallucinogenic psychoactive drugs failed to shift the dose-response patterns of pausing for DOM or LSD. Depletion of brain catecholamines by pretreatment with intraventricular 6-OHDA reduced baseline FR-40 rates and attenuated the disruptive effects of d-amphetamine, but failed to modify the dose-response patterns of indole and phenethylamine hallucinogens. On the other hand, pretreatment with intraventricular 5,7-DHT to deplete brain 5-HT potentiated the pause-producing effects of the hallucinogens, although the disruptive effects of phenobarbital were not altered by this pretreatment. Injection of 5,7-DHT into the medial forebrain bundle at the hypothalamic level slightly potentiated LSD, attenuated DOM, and did not affect the pausing produced by mescaline. Metergoline pretreatment shifted the LSD and DMT dose-response curves for pausing to the right by a factor of 2--3, but shifted the DOM and mescaline dose-response patterns to a much greater extent. Metergoline alone slightly increased FR-40 response rates and decreased pausing from baseline levels. The patterns of imparied FR-40 performance induced by d-amphetamine and phenobarbital were unaltered by pretreatment with metergoline. The indole and phenethylamine classes of hallucinogens appear to disrupt this behavior by an agonistic effect at central 5-HT receptors. However, the two classes of drugs may interact with brain 5-HT systems by somewhat different mechanisms.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗