The effect of repeated-intermittent exposure to 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) during adolescence on learning and memory in adult rats.

BACKGROUND: According to the European Drug Report, the use of novel psychoactive substances (NPS) is constantly growing. NPS are widely abused by human adolescent subjects. 5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is one of the most frequently used hallucinogenic NPS. 5-MeO-DIPT intoxication results in hallucinations, vomiting, and tachycardia. Long-term exposure to 5-MeO-DIPT was reported to lead to development of post-hallucinogenic perception disorder. The aim of the present study was to determine whether repeated-intermittent administration of 5-MeO-DIPT during adolescence affects learning and memory in adult rats. METHODS: Rats were treated with 5-MeO-DIPT in a dose of 2.5mg/kg from 30 to 33 and 37 to 40 Postnatal Day (PND). The experiments were conducted when the animals reached 90 PND. The effect of 5-MeO-DIPT on cognitive functions was assessed using the novel object recognition, open field, and serial pattern learning (SPL) tests. RESULTS: Repeated-intermittent exposure to 5-MeO-DIPT during adolescence decreased the number of crossings in the open field test at adulthood. Moreover, 5-MeO-DIPT treatment impaired adult rats' learning in the SPL test. There was no change in the novel object recognition test. CONCLUSIONS: The present results show that the performance of adult rats treated with 5-MeO-DIPT during adolescence was impaired in the open field test, which indicates the attenuated exploratory activity. 5-MeO-DIPT treatment undermined adult rats' performance in the serial pattern learning test, suggesting impairment of long term memory and cognitive flexibility. The present study showed that the exposure to 5-MeO-DIPT during adolescence might lead to long-lasting behavioral changes which persisted long after the exposure period.

Comparative efficacy and the window of radioprotection for adrenergic and serotoninergic agents and aminothiols in experiments with small and large animals.

This review gives a comparative evaluation of the radioprotective properties and the therapeutic index (TI) of radioprotectors from various pharmacological group in experiments on both small and large animals. It presents a hypothesis explaining the decrease in the TI of cystamine and 5-methoxytryptamine (mexamine), and the retention of that of α1-adrenomimetic indralin, and also compares the effects on large and small animals. The considerable differences in the therapeutic indices of catecholamines, serotonin and cystamine are a consequence of specific features of their mechanisms of radioprotective action. Radioprotectors acting via receptor mediation tend to provide a more expanded window of protection. The reduction in the TI of cystamine in larger animals, such as dogs, may be caused by the greater increase in toxicity of aminothiols in relation to the decrease in their optimal doses for radioprotective effect in going from mice to dogs, which is a consequence of the slower metabolic processes in larger animals. The somatogenic phase of intoxication by cystamine is significantly longer than the duration of its radioprotective effect, and increases with irradiation. The decrease in the radioprotective effect and the TI of mexamine in experiments with dogs may be caused by their lower sensitivity to the acute hypoxia induced by the mexamine. This is because of lower gradient in oxygen tension between tissue cells and blood capillaries under acute hypoxia that is determined by lower initial oxygen consumption in a large animal as compared with a small animal. Indralin likely provides optimal radioprotective effects and a higher TI for large animals via the increased specificity of its adrenergic effect on tissue respiration, which supports the development of acute hypoxia in the radiosensitive tissues of large animals. The stimulatory effect of indralin on early post-irradiation haematopoietic recovery cannot provide a high level of radioprotective action for large animals, but it may promote recovery.

Cancer as the main aging factor for humans: the fundamental role of 5-methoxy-tryptamine in reversal of cancer-induced aging processes in metabolic and immune reactions by non-melatonin pineal hormones.

Aging and advanced cancer are characterized by similar neuroendocrine and immune deficiencies; the most important of them consist of diminished nocturnal production of the pineal hormone melatonin (MLT) and decreased production of IL-2. At present, however, it is known that the pineal gland may produce indole hormones other than MLT. The most investigated of them is represented by 5-methoxy-tryptamine (5-MTT), which may exert antitumor, anticachectic, and immunomodulating effects under experimental conditions, in addition to those effects produced by MLT itself. In an attempt to obtain some preliminary data in human subjects about the potential therapeutic properties of 5-MTT, three different studies of 5-MTT have been carried out in advanced solid tumor patients. The first study of MLT plus 5-MTT included 14 thrombocytopenic cancer patients who did not respond to MLT alone. In the second study we have compared the clinical efficacy of MLT plus 5-MTT in a group of 25 untreatable metastatic cancer patients to the results obtained in a control group of 25 cancer patients receiving MLT alone. Finally, the third study of MLT plus 5-MTT included 14 untreatable metastatic cancer patients who did not respond to MLT alone. In all of these studies, MLT and 5-MTT were given orally at the level of 20 mg/day in the evening and at 5 mg/day during the period of maximum light. A normalization of platelet number was achieved by MLT plus 5-MTT in 5 of 14 (36%) thrombocytopenic cancer patients who did not respond to MLT alone. The percentage of disease control obtained by MLT plus 5-MTT in untreatable metastatic cancer patients was significantly higher than that achieved by MLT alone (15/25 [60%] vs. 8/25 [32%], P < 0.05). Finally, the association of 5-MTT with MLT induced disease stabilization in 4 of 14 (29%) untreatable metastatic cancer patients who did not respond to MLT alone.

Principles of psychoneuroendocrinoimmunotherapy of cancer.

Recent advances in the knowledge of the mechanisms responsible for antitumor immunity have stimulated the elaboration of new cancer immunotherapeutic strategies. Moreover, more recent discoveries have demonstrated that immune responses are under a physiological modulatory control played by several neuroendocrine pathways, which explain the differences between the in vivo and in vitro immune responses. While until a few years ago the evaluation of the immune status of cancer patients was substantially established on the basis of clinical empirical criteria, recent discoveries of the antitumor cytokine network have allowed the biochemical bases of anticancer immunity to be defined, leading to new anticancer immunotherapeutic strategies, on the basis of patient neuroendocrine and neuroimmune status, in an attempt to correct the great number of cancer-related alterations on the basis of knowledge of the physiopathology of anticancer immunity. The rationale for cancer neuroimmunotherapy consists of the possibility to enhance the efficacy of the various immunotherapeutic strategies by a concomitant administration of antitumor cytokines (namely IL-2), in addition to neuroendocrine endogenous molecules (namely the pineal indole hormones), able to stimulate the anticancer immunoresponse by amplifying the anticancer reaction and/or by counteracting the generation of immunosuppressive events.

[Radioprotective properties of indralin combined with cystamine and mexamine].

The study of indralin radioprotective properties at its joint application with cystamine and mexamine was carried out in the experiments on inbred mice and rats. The mice and rats were exposed to whole-body y-irradiation at a dose of 9.0 and 9.5 Gy, correspondingly. A combined parenteral administration ofindralin and cystamine at a dose of 25 mg/kg showed ponentiaton of indralin radioprotective properties up to a level of the ED50 effect versus the absence of or a weak radioprotective effect in the case of their separate application. In the experiments on rats, indralin (50 mg/kg) and mexamine (12 mg/kg) injected intraperitoneally almost completely eliminated the animal mortality from the intestinal syndrome of acute radiation sickness amounting in the control radiation group to 60% on the 7th day after exposure to radiation at a dose of 9.5 Gy. However, at the above conditions, radioprotectors at these doses had a low-level radioprotective action at the onset of the bone marrow syndrome of acute radiation sickness. Combined application of indralin and mexamine at the same doses and at the same conditions led to a radiation protection 50% as high as in the case when radioprotectors were applied separately at a double dose.

[Protective action of radioprotectors and shielding against high-energy protons in experiments with rats].

Experiments with male rats were staged to study effectiveness of radioprotectors of two classes of chemical compounds (aminothiols--cystamine and indolyl alkylamines--mexamine and indralin) against high-energy protons (120 MeV) at a minimal absolutely lethal dose (10 Gy) and more than lethal doses (11.0-14.0 Gy). The best protective effect was provided by intraabdominal indralin at a dose of 75 mg/kg. However, this protective effect of indralin weakens with a dose rise and fades away with the dose rising to the absolutely lethal or more than lethal level (14.0 Gy). Investigations of the effectiveness of shielding different segments of the rat's body from high-energy protons (120 MeV) at more than lethal doses showed a substantial reduction and then full loss of the shielding protective action. Evaluation of the effectiveness of combined protection (radioprotectors plus shielding) against high-energy protons at more than lethal doses led to the conclusion about an additive (at 1.0-13.0 Gy) or potentiative (at 14.0 Gy) effect. For instance, indralin (75 mg/kg) and shielding of the abdomen increased rat's survivability to 89.7% after exposure at 11.0-13.0 Gy and to 87.5% after exposure at 14.0 Gy. It should be kept in mind that the radioprotective action of this combination was also observed during exposure to more than lethal doses when the protective effect of shielding and chemical compounds is minimal or lost altogether.

Intraocular microinjections repair experimental Parkinson's disease.

Circadian involvement in Parkinson's disease (PD) and more specifically in nigro-striatal dopamine (NSD) function is of increasing interest to the neurosciences. Given that bright light therapy is of therapeutic value in PD, possible mechanisms underlying retinal involvement in this phenomenon was explored further by administering anti-Parkinsonian chemotherapies into the vitreus humour directly adjacent to the retina. 2 microl of a 100 mM solution of L-Dopa significantly improved motor function in the later stages of degeneration and during the day while the injection of 2 microl of a 10 mM solution of the melatonin receptor antagonist ML-23 improved motor function in the early stages of PD and during the dark phase of the light/dark cycle. The results suggest that the function of nigral cells is regulated by a more global system embracing circadian physiology that extends from the retina to the pineal. Furthermore, the induction of PD is characterised by an imbalance between melatonin and dopamine (DA) whereby this ratio is elevated at least 6 to 1 in favour of melatonin. The commonly observed treatment failures and side effects of DA replacement therapy probably result from increasing endogenous DA without taking parallel melatonin dysfunction into account. The proposed integrated function of the NSD and circadian systems may permit therapeutic targeting at a level which is safer, more effective and without the side effects of systemically administered regimens of DA replacement.

Perinatal exposure to 5-methoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat.

Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models, and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to, pregnant dams from gestational days 12 to 21 (1mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5mg kg s.c.), induce in the adolescent rat offspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity and rearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimming in the forced swim test. Acute administration of LY 228729 (1.5mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activity in the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposed offspring. Co-administration of WAY 100635 (0.25mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in the adolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action on presynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds.

An examination of the effects of 5-Methoxy-n, n-di(ISO)propyltryptamine hydrochloride (Foxy) on cognitive development in rats.

The hallucinogenic "designer drug" known as Foxy or Methoxy Foxy and formally know as 5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride (5-MeO-DIPT) is rapidly gaining popularity among recreational users. However, little is known about the consequences of its use on neuropsychological development or behavior. During one of two adolescent periods, the rats were given repeated injections of either saline or 5 mg/kg of 5-MeO-DIPT. Once the animals reached 80 days of age, they were trained and tested on a number of tasks designed to assess the effects of 5-MeO-DIPT, if any, on memory tasks with spatial components that presumably involve declarative memory systems and on a nonspatial task that is considered sensitive to disruptions in nondeclarative memory. With one exception, both the 5-MeO-DIPT- and saline-treated rats were able to master the spatial navigation tests at comparable rates. However, the performance of the drug-treated rats was markedly inferior to that of the control animals on a response-learning task, suggesting a lack of flexibility in adapting their responses to changing task demands. This could indicate reductions in serotonin activity in the forebrain similar to the effects of studied drugs such as methylenedioxymethamphetamine (MDMA), suggesting 5-MeO-DIPT may act as a toxin compromising serotoninergic systems in the brain.

Total pineal endocrine substitution therapy (TPEST) as a new neuroendocrine palliative treatment of untreatable metastatic solid tumor patients: a phase II study.

OBJECTIVES: It is known since many years that the pineal gland plays an anticancer role, and melatonin (MLT), the most investigated pineal hormone, has been proven to exert antitumor activity. However, MLT would not be the only hormone responsible for the antitumor action of the pineal gland. In fact, recent advances in the pineal investigations have shown that pineal indoles other than MLT may also exert anticancer activity, namely the three main indoles, consisting of 5-methoxytriptamine (5-MTT), 5-methoxytryptophol (5-MTP) and 5-methoxy-indole acetic acid (5-MIA). Cancer progression has appeared to be associated with a concomitant decline in the pineal endocrine function. Therefore, the replacement of a complete pineal function in the advanced cancer patients would require the exogenous administration of the overall four pineal indoles. Several clinical studies have shown that MLT alone at pharmacological doses may induce a control of the neoplastic progression in about 30% of untreatable metastatic solid tumor patients. The present study was performed in an attempt to evaluate the therapeutic of a total pineal endocrine substitution therapy with its four indole hormones in cancer patients, for whom no other conventional therapy was available. METHODS: The study included 14 metastatic solid tumor patients, who had failed to respond to the conventional anticancer therapies. The pineal indoles were given orally according to a schedule elaborated in an attempt to reproduce their physiological circadian secretion during the daily photoperiod. MLT was given at 20 mg/day during the night, whereas the other indoles were given at 1 mg/day, by administering 5-MIA in the morning, 5-MTP at noon and 5-MTT in the afternoon. RESULTS: A disease-control was achieved in 9/14 (64%) patients, consisting of partial response (PR) in one patient and stable disease (SD) in the other 8 patients. The median time of disease-control (PR + SD) was 6 months (range: 4-10). CONCLUSIONS: This preliminary study shows that a total pineal endocrine replacement therapy by an exogenous administration of the overall four pineal indoles may induce a disease-control in about 60% of untreatable metastatic solid tumor patients. Then, these results would be clearly superior with respect to those described with MLT alone, by confirming in humans that MLT is not the only hormone responsible for the anticancer property of the pineal gland. Since Cartesius was the first author who suggested the fundamental role of the pineal in the connection between consciousness and biological life, this therapy could be defined as a Cartesian therapy.

Foxy, a designer tryptamine hallucinogen.

Foxy is slang for 5-methoxy-N,N-diisopropyltryptamine. It has hallucinogenic properties, similar to other tryptamine compounds, and is mildly euphoric. This case report describes a 21-year-old Caucasian man who ingested a pill called Foxy containing an unknown amount of drug. He was observed in hospital for 2 h, during which time he had mild hallucinations and could not move his limbs. A urine sample was collected approximately 4 h after drug ingestion. The patient was then discharged with no follow up assessment. The 5-methoxy-N,N-diisopropyltryptamine was identified in the urine by gas chromatography-mass spectrometry. Standards prepared from the pure material were used in the identification. Quantitative analysis using the same analytical technique resulted in a urinary concentration of 1.7 micro g/mL. Through oxidative deamination, the metabolite, 5-methoxy-indole acetic acid, was formed. It was identified in the urine, and the concentration was determined to be 1.3 micro g/mL using gas chromatography-mass spectrometry. Two other compounds were discovered in the urine sample as a result of a routine drug screen. From their mass spectra, they were tentatively identified as 5-methoxy-N-isopropyltryptamine and 5-methoxy-N,N-diisopropyltryptamine-N'-oxide.

Modulation of anticancer cytokines IL-2 and IL-12 by melatonin and the other pineal indoles 5-methoxytryptamine and 5-methoxytryptophol in the treatment of human neoplasms.

Lymphocyte number still remains one of the most important immune parameters predicting the prognosis of advanced cancer patients. IL-2 and IL-12 are the main antitumor cytokines in humans, and their effect is modulated by the neuroendocrine system, mainly by the pineal gland through the circadian release of melatonin (MLT) and perhaps that of other indole hormones, such as 5-methoxytryptamine (5-MTT), and 5-methoxytryptophol (5-MTP). MLT has been proven to exert important antitumor immunomodulating effects, whereas the possible immunomodulatory properties of the other pineal indoles are still controversial. In an attempt to better define the pineal neuroendocrine regulation of the anticancer cytokine network, we have evaluated in metastatic solid-tumor patients the effects on lymphocyte number induced by different neuroimmune regimens, consisting of MLT alone (20 mg/day orally in the evening), subcutaneous (s.c.) low-dose IL-2 alone (3 MIU/day in the evening for 6 days/week), s.c. low-dose IL-12 alone (0.5 mcg/kg once/week in the morning), IL-12 plus MLT, IL-2 plus MLT, and IL-2 plus MLT plus 5-MTT (10 mg/day orally in the afternoon) plus 5-MTP (5 mg/day orally at noon). The results showed the following evidence: (1) MLT alone is unable to induce lymphocytosis; (2) MLT significantly enhances IL-2-induced lymphocytosis; (3) IL-12 alone determines lymphocytopenia, which can be reversed by MLT; (4) IL-2 plus IL-12 induces a very pronounced lymphocytosis, which can be further amplified by MLT; (5) a total pineal endocrine replacement therapy with MLT, 5-MTT, and 5-MTP further increases IL-2-induced lymphocytosis with respect to MLT plus IL-2 alone. Therefore, this study confirms that IL-2- and IL-12-dependent anticancer immunity is under a pineal modulation.

Hypotensive activity of the pineal indoleamine hormones melatonin, 5-methoxytryptophol and 5-methoxytryptamine.

Injection of the pineal indoles melatonin, 5-methoxytryptophol and 5-methoxytryptamine via the external jugular vein elicited a dose-dependent depression in mean arterial pressure. Melatonin and 5-methoxytryptophol were approximately equipotent and a dose of 150 micromol/kg brought about a reduction of about 40 mmHg in mean arterial pressure. Methoxytryptamine exerted a much more potent hypotensive action. An abrupt decrement in mean arterial pressure by 30 mmHg occurred when the dose was only 2 nmol/kg. Subsequent increases in the dose further lowered the mean arterial pressure, but more gently. The other pineal indoles tested including 5-methoxyindoleacetic acid and 5-hydroxyindoleacetic acid, as well as 6-methoxy-2-benzoxazolinone, did not affect the mean arterial pressure when tested up to 80 micromol/kg. Methylene blue, a guanylate cyclase inhibitor, was not able to antagonize the hypotensive activity of melatonin, suggesting that the mechanism of action of melatonin does not involve guanylate cyclase. Lidocaine, which blocks sodium channels in perivascular nerves, antagonized the hypotensive action of melatonin.

Modification of the anxiolytic action of 5-HT1A compounds by GABA-benzodiazepine agents in rats.

The general purpose of the present study was to analyze the possible interactions between the GABA benzodiazepine and the serotonin systems in the mediation of the antianxiety actions of 5-HT1A compounds. The anxiolytic effect of buspirone (5 mg/kg), ipsapirone (5 mg/kg), indorenate (5 mg/kg), and 8-OH-DPAT (0.5 mg/kg) was established in the rat burying behavior test. Flumazenil (5 mg/kg), but not bicuculline (2.5 mg/kg), effectively counteracted the reduction in burying behavior produced by buspirone, ipsapirone, and 8-OH-DPAT. These same 5-HT1A compounds, at subthreshold doses, produced an important reduction in burying behavior when combined with diazepam (0.25 mg/kg). The effect of indorenate was not altered by any of the antagonists and, when combined with diazepam it produced large increases in burying behavior latency. Only buspirone alone and in combination with bicuculline or flumazenil impaired motor coordination as tested in the rota rod. Data are discussed on the bases of the interaction between the GABAergic and serotonergic systems, stressing species differences and variations due to the animal model of anxiety.

Evidence that the secretory response of rat intestine to 5-hydroxytryptamine in-vivo involves more than one 5-hydroxytryptamine-receptor subtype.

The transintestinal potential difference (PD) across rat mid-small intestine and proximal colon was measured in-vivo. The 5-hydroxytryptamine (5-HT)-induced increase in PD, which reflects a stimulation of electrogenic C1 secretion, was mimicked by both 2-methyl-5-hydroxytryptamine (2-CH3-5-HT), an agonist at 5-HT3 receptors, and 5-methoxytryptamine (5-MT), an agonist that lacks affinity for 5-HT3 receptors. The 5-HT3 antagonist granisetron caused a marked inhibition of the response to 2-CH3-5-HT in both regions, but only produced a small inhibition of the small intestinal response to 5-HT, with a more pronounced effect in the colon. The failure of granisetron to produce a marked antagonism of the 5-HT-induced rise in the transintestinal PD, coupled with the ability of 5-MT to induce a secretory response, indicates that 5-HT3 receptors are not the only ones involved in the stimulation of C1 secretion. The 5-HT2 antagonist ketanserin failed to influence the response to 5-HT in either the small intestine or the colon, but it did inhibit the action of 5-MT, having a much greater effect in the small intestine. In the presence of granisetron however, ketanserin also inhibited the small intestinal response to 5-HT, having only a minimal effect in the colon. This suggests that 5-HT2 receptors can also play a role in the activation of C1 secretion. These observations suggest that both 5-HT2 and 5-HT3 receptors contribute to the stimulation of electrogenic C1 secretion by 5-HT, with 5-HT2 receptors playing a more prominent role in the small intestine and 5-HT3 receptors being more important in the colon.

[Evaluation of the toxicity of indorenate on reproduction]. / Evaluación de la toxicidad del indorrenato sobre la reproduccion.

Indorenate (TR3369) a new antihypertensive drug, was examined for effects upon general reproductive performance, for peri-postnatal and embryofetal toxicity in the rat at doses of 0, 10, 20, 40 and 60 mg/kg/day by oral administration. Excluding the 60 mg/kg dose, in the fertility study, any dose produced neither decrement of body weight gain of progenitors, fertility, fetal weight nor survival rate. Retardation of the surface righting, pinnal unfolding or startle response were not observed. On the other hand, 40 and 60 mg/kg significantly increased the number of resorptions. In the peri-postnatal study, doses of 40 and 60 mg/kg incremented the number of dead pups at birth, and the later also affected the survival rate, growing and air righting reflex. Reproductive performance of the F1 offsprings was unimpaired. Indorenate in contrast to serotonin, from which it is a structural derivative, gave no evidence of teratogenicity when administered during the period of organogenesis. It was concluded that the parameters of fetal development were not affected by doses of up to 20 mg/kg, which represents approximately 1200 times the proposed dose for hypertensive patients.

Do 5-HT4 receptors mediate the intestinal secretory response to 5-HT in rat in-vivo?

The involvement of the recently characterized 5-HT4 receptor in the actions of 5-hydroxytryptamine (5-HT) on jejunal, ileal and colonic electrogenic ion secretion was investigated in the rat in-vivo. 5-HT and the 5-HT1-, 5-HT2- and 5-HT4-receptor agonist 5-methoxytryptamine (5-MeOT), induced a rise in transintestinal PD in all regions of the gut. However, the 5-HT4-receptor agonists renzapride and cisapride had no effect. Furthermore, the 5-HT4-receptor antagonists SDZ 205-557 (2-diethylaminoethyl-[2-methoxy-4-amino-5-chloro] benzoate), tropisetron and SB 204070 ([1-butyl-4-piperidinylmethyl]-8-amino-7-chloro-1,4- benzodioxan-5-carboxylate hydrochloride) did not affect the secretory response to either 5-HT or 5-MeOT in the jejunum, but did cause a small inhibition in the ileum and colon. It is concluded that 5-HT4 receptors do not make a contribution to the electrically monitored 5-HT intestinal secretory response in the rat jejunum in-vivo, but may play a small role in the ileum and colon.

[Protective action of mexamine and indralin in intensive electromagnetic irradiation of rats]. / Zashchitnaia aktivnost' meksamina i indralina pri intensivnom élektromagnitnom obluchenii krys.

Protective properties of radioprotectors from indolyl alkylamine group (mexamine and indralin) in rats exposed to powerful electromagnetic irradiation (2.4 GHz, specific absorption rate 90-100 W/kg) was studied. The survival index of tested animals reached the maximum in condition of prophylactic administration of drugs in intervals 20-60 minutes before irradiation. Protective effect of mexamine and indralin connected with hypothermia and desensitization conditioned by the drugs use.

Types of serotonergic receptors involved in the control of reticulo-ruminal myoelectric activity in sheep.

The effects of peripheral (intravenous, i.v.) and central (intracerebroventricular, ICV) administration of agonists of 5-HT1A, 5-HT2, 5-HT3 and 5-HT4 receptors were investigated in conscious sheep chronically fitted with intraparietal electrodes on the reticulum and the dorsal, ventral and caudo-ventral rumen. The 5-HT1A agonist 8-hydroxydipropylaminotetralin increased reticular and decreased ruminal spike burst frequency when given i.v. (80 micrograms/kg) and ICV (8 micrograms/kg). The 5-HT2 and 5-HT3 agonists, alpha-methylserotonin and 2-methylserotonin, induced a moderate inhibition of rumino-reticular contractions when given i.v. at 100 and 150 micrograms/kg, respectively, while marked inhibition was observed after ICV administration at doses of 10 and 5 micrograms/kg, respectively. The 5-HT4 agonist 5-methoxytryptamine strongly stimulated rumino-reticular motility by the ICV (10 micrograms/kg) route, whereas it induced a moderate inhibition when administered i.v. (200 micrograms/kg). The selective antagonist of 5-HT1A, 5-HT2, 5-HT3 and 5-HT4 receptors, spiroxatrine, ritanserin, granisetron and DAU 6285, respectively, blocked the responses of the respective agonists given by the same route. Moreover, the antagonists given ICV blocked the effects of the agonists given i.v. except for DAU 6285 ICV, which did not antagonize the inhibition induced by 5-methoxytryptamine i.v. It is concluded that the four types of serotonergic receptors investigated control rumino-reticular motility at the central level. However, according to the receptor type and the forestomach area (reticulum or rumen) this control may be stimulatory or inhibitory, demonstrating a pleiotropic role of serotonin in the control of rumino-reticular motility in sheep.