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Biomedical subjects

R H Rech

Publications and source records attributed to R H Rech.

At least 55 records · Page 3Linked to original sources
PubMed1981

Comparison of anti-conflict drug effects in three experimental animal models of anxiety.

A novel form of experimentally-induced conflict behavior based on the conditioned suppression of drinking (CSD) is described and compared with two conventional animal models of human anxiety--a modified Geller-Seifter and an Estes-Skinner (Conditioned Emotional Response) procedure. The CSD procedure offered significant advantages over the two operant procedures in that the session duration was short (10 min) and the acquisition of stable behavioral baselines was rapid (approximately 2 weeks). Like the more conventional procedures, the CSD paradigm permitted the simultaneous determination of drug effects on shock-suppressed and nonsuppressed responding as estimates of antianxiety and sedative properties, respectively. With the CSD procedure, the anticonflict profiles for the benzodiazepines were highly correlated with their relative clinical antianxiety potency. Therefore, the CSD procedure appears to be a valuable tool in screening for possible antianxiety agents as well as in the behavioral testing of mechanism of action hypotheses regarding such agents.

Animals↗
PubMed1981

Central 5-hydroxytryptamine and the effects of hallucinogens and phenobarbital on operant responding in rats.

The present study was designed to examine the role of 5-hydroxytryptamine (5-HT) neurons in the behavioral effects of d-lysergic acid diethylamide (LSD), an indolealkylamine hallucinogen, 2.5-dimethoxy-4-methylamphetamine (DOM) and mescaline, phenethylamine hallucinogens, and phenobarbital, a non-hallucinogen. Male rats, maintained at 70-80% of their free-feeding weights, were trained to press a lever for food pellet reinforcement on a fixed ratio-40 operant schedule. When trained, these rats responded at a constant, rapid rate (approximately 100 responses/min) during daily 40 min test sessions. Administration of hallucinogens caused an abrupt cessation of responding (a "pause"), for some portion of the session. The duration of this pause was dose-dependent for LSD (12.5-100 micrograms/kg), DOM (0.125-1.0 mg/kg) and mescaline (7.1-14.2 mg/kg). On the other hand, phenobarbital (12.5-50 mg/kg) did not cause pausing, but resulted in slowed, erratic intrasession response rates. When the same tests were repeated in rats that had previously received an intracerebroventricular injection of 5,7-dihydroxyptamine (5,7-DHT) the dose-response curves for the pausing induced by all three hallucinogens were shifted to the left, while the behavioral disruption produced by phenobarbital was unaltered. In these animals the 5-HT but not the norepinephrine concentrations was markedly reduced in all brain regions examined. These results suggest that 5-HT neurons are involved with the behavioral effects of hallucinogens but not of phenobarbital.

5,7-Dihydroxytryptamine↗
PubMed1981

The effect of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM), pentobarbital and methaqualone on punished responding in control and 5,7-dihydroxytryptamine-treated rats.

The purpose of the present study was to determine the role of central 5-hydroxytryptamine (5-HT) neuronal systems in the effects of d-lysergic acid diethylamide (LSD), 2,5-methoxy-4-methylamphetamine (DOM), pentobarbital (PB) and methaqualone (MQ) on punished responding in rats. Water-deprived rats were trained to drink from a tube that was electrified at intervals (variable interval 21 sec; 0.03 mA current intensity), electrification being signalled by a tone. In daily 10-min control sessions, these animals accepted a relatively constant number of shocks; water consumption was also quite stable. At maximally effective doses PB, and to a lesser extent MQ, produced large (400-600 percent of control) increases in punished responding with little decrease in water intake. Higher doses of these agents produced a significant depression of unpunished responding (water intake). The hallucinogens, on the other hand, produced only moderate (125-175 percent of control) increases in the number of shock received, yet a similar depression of unpunished responding. Selective destruction of 5-HT neurons by intracerebroventricular administration of the neurotoxin 5,7-dihydroxytryptamine per se produced little change in the number of shocks received or water consumed in controls sessions. This destruction of 5-HT neurons failed to alter the effects of PB or MQ on punished or unpunished responding. The increase in punished responding produced by the hallucinogens, however, was blocked by this destruction of 5-HT neurons. Furthermore, the capacity of the hallucinogens to decrease water intake was significantly potentiated by the neurotoxin pretreatment. These data demonstrate that the effects of the hallucinogens LSD and DOM on conditioned suppression are quite different from those of PB and MQ, and that this difference may be due to the extent of 5-HT involvement in the effects of these agents.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1981

Antagonism of the behavioral effects of 2,5-dimethoxy-4-methylamphetamine (DOM) and quipazine by metergoline.

The present study examined the disruptive effects of the phenethylamine hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) and the putative 5-hydroxytryptamine (5-HT) agonist quipazine on fixed ratio-40 (FR-40) operant responding alone or after pretreatment with putative 5-HT antagonist metergoline. Food-deprived male rats were trained to bar press on a FR-40 schedule for food reinforcements; control responding under this schedule is characterized by a rapid, constant rate of responding (approximately 100 response/min). In control animals, both DOM and quipazine produced dose-dependent disruptions of FR-40 performance characterized by periods of non-responding or "pausing". Following pretreatment with 1.0 mg/kg, and to a lesser extent 0.1 mg/kg, metergoline (180 min prior to the session) the dose-response curves for the "pausing" produced by both DOM and quipazine were shifted significantly to the right. Moreover, increasing the dose of DOM about 16-fold and that of quipazine about 8-fold appears to completely override the antagonism by 1 mg/kg metergoline. These results suggest that the "pausing" produced by DOM or quipazine is the result of activation of 5-HT receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1981

The behavioral effects of hallucinogens in rats following 5,7-dihydroxytryptamine administration into the medial forebrain bundle.

The hypothesis that 5-hydroxytryptamine (5-HT) neurons and/or receptors are involved in the mechanism of action of hallucinogens is supported by the fact that intraventricular administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) selectively destroys central 5-HT neurons in the brain and potentiates the behavioral effects of lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM) and mescaline. The locus in the brain where this potentiation might occur is not known. In the present experiment, the medial forebrain bundle (MFB) was studied because it is the primary tract containing fibers from the cell bodies in the raphe nuclei to forebrain structures receiving 5-HT input. Male rats received 5,7-DHT (6 micrograms/2 microliter) or vehicle injections bilaterally into the MFB; this procedure caused a significant reduction of 5-HT in the cortex, hippocampus and hypothalamus of lesioned rats, but not in the striatum. Regional dopamine and norepinephrine concentrations were not affected by this treatment. The behavioral effects of the hallucinogens were tested in a situation in which the animals pressed a bar under a fixed ratio-40 (FR-40) schedule of food reinforcement. The disruptive effects of LSD on responding were enhanced in the 5,7-DHT-treated animals, while the effects of DOM were diminished; there was no change in the response to mescaline. These data suggest that, while 5-HT neurons are involved in the behavioral effects of hallucinogens, the precise sites and/or mechanisms of action of LSD, DOM and mescaline may differ.

5,7-Dihydroxytryptamine↗
PubMed1980

The effects of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM) and d-amphetamine on operant responding in control and 6-hydroxydopamine-treated rats.

The purpose of the present study was to determine the role of central catecholaminergic neuronal systems in the effects of LSD, DOM and d-amphetamine on fixed ratio (FR) operant responding in rats. Food-deprived male rats were trained to press a bar for food reinforcement on a FR-40 schedule. Control responding on this schedule is characterized by a rapid, constant rate of responding (approximately 100 responses/min) throughout a 40 min test session. LSD and DOM, as with other hallucinogens, produced dose-dependent periods of nonresponding or "pausing," followed by reinstatement of responding at or near the control rate. Administration of the non-hallucinogen, d-amphetamine, did not produce "pausing," but caused the response rate to slow and become erratic. In animals pretreated intraventricularly with 6-hydroxydopamine (6-OHDA; 200 micrograms/10 microliter X 2), the response to LSD and DOM was unchanged, while the response to d-amphetamine was significantly diminished. The neurotoxin significantly decreased brain catecholamines to less than 25 percent of control in al regions examined, without altering 5-HT concentrations in these same regions. These data demonstrate that the effects of LSD and DOM on FR-40 responding are quite different from those of d-amphetamine, and that this difference may be due to the extent of catecholamine involvement in the effects of these agents.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1980

Naloxone potentiates the disruptive effects of mescaline on operant responding in the rat.

Food-deprived male rats were trained to press a lever on a fixed ratio-40 (FR-40) operant schedule for food reinforcement. Administration of mescaline (4.0--10.0 mg/kg) immediately before the start of the operant session resulted in a cessation of responding for some portion of the 40-min period ("hallucinatory pause"). The duration of this pause was found to be dose-dependent. Although administration of naloxone alone (1.0-8.0 mg/kg, five minutes prior to the start of the session) had no effect on FR-40 responding per se, pretreatment with this agent significantly potentiated the disruptive effects of mescaline. This potentiation by naloxone was further shown to be dose-dependent. These data suggest that the effects of the phenethylamine hallucinogen mescaline are potentiated by pretreatment with the narcotic antagonist naloxone.

Animals↗
PubMed1980

Enhancement of the behavioral effects of 2,5-dimethoxy-4-methyl-amphetamine (DOM) by pretreatment with p-chlorophenylalanine.

Seven food deprived male rats were trained to press a bar on a fixed ratio-40 (FR-40) schedule of food reinforcement. Administration of 0.5 mg/kg 2,5-dimethoxy-4-methyl amphetamine (DOM) immediately before the start of the session resulted in cessation of responding for some portion of the 40-min test session. Three successive days of p-chlorophenylalanine (PCPA) administration (100 mg/kg) 30 min after each session reduced 5-hydroxytryptamine (5-HT) to 15-26% of control concentrations in various brain regions but did not alter control rates of responding under the FR-40 schedule. Administration of 0.5 mg/kg DOM following this PCPA pretreatment resulted in a greater amount of nonresponding than observed earlier. These data suggest that the effects of the phenethylamine hallucinogen DOM are enhanced by disruption of 5-HT neuronal activity.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1980

Methadone exposure in utero: effects on brain biogenic amines and behavior.

Gravid rats were treated with methadone, 10 mg/kg/day, or vehicle, from day 5 of gestation to term. The offspring were nursed by foster mothers receiving either methadone or vehicle to form 4 groups: (A) methadone during gestation and lactation, (B) methadone during gestation, (C) methadone during lactation, and (D) no drug treatment. Brain monoamines and metabolites were examined at 21 days of age and found to be decreased in groups A and B. Animals treated comparably to group B and sacrificed at 90 days of age showed no abnormalities in brain monoamines excepting a decrease in dopamine metabolites in limbic areas. Another group treated in utero with methadone was tested at 90 days fo age for shuttle-box avoidance acquisition using massed trials. Methadone-exposed subjects exhibited more avoidances, escapes and intertrial shuttles than controls by the third day of training. These results suggest that subtle but lasting changes in limbic dopamine functions as a consequence of fetal exposure to methadone may make rats hyper-responsive in a massed-trial avoidance procedure in the shuttle-box.

Animals↗
PubMed1978

The effect of indoprofen on phenylquinone-writhing and prostaglandin synthesis.

The ability of indoprofen or sodium indoprofen to inhibit phenylquinone-writhing and renal prostaglandin synthesis was determined in mice following a single oral dose of either drug. Male mice (4/group) were treated with 1.5 mg/kg indoprofen or sodium indoprofen. Inhibition of phenylquinone-writhing was determined at 2, 4, 8, 16 and 32 hr post treatment. Animals were sacrificed and blood collected for determination of plasma indoprofen concentration. Kidneys were removed and prepared for determination of renal prostaglandin synthesis by an in vitro technique. Phenylquinone-writhing was significantly depressed by both preparations at 2 and 4 hr post treatment. Sodium indoprofen also significantly depressed writhing at 8 hr post treatment. Renal prostaglandin synthesis, like phenylquinone-writhing, was significantly depressed at 2 and 4 hr after drug treatment. Plasma indoprofen concentration was correlated with both inhibition of phenylquinone-wrighing and inhibition of renal prostaglandin synthesis. When writhes were plotted versus prostaglandin synthesis, a positive correlation was observed suggesting a temporal relationship between inhibition of phenylquinone-writhing and inhibition of renal prostaglandin synthesis.

Analgesics↗