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R H Rech

Publications and source records attributed to R H Rech.

At least 37 records · Page 2Linked to original sources
PubMed1985

Mechanisms of the initial treatment phenomenon to diazepam in the rat.

The initial treatment phenomenon (ITP) to diazepam was investigated using a conditioned suppression of drinking (CSD) paradigm. Female Sprague-Dawley rats were trained to a stable baseline of punished and unpunished responses in the CSD paradigm. In Experiment 1, a control group (1) received vehicle after the CSD session on each of seven drug test days, while group 2 was treated with 3.0 mg/kg diazepam IP after each of these sessions. On drug test days 8-12, diazepam was administered to both groups before the CSD session. Drug test days were separated by 2-3 days when the animals were untreated but performed in the CSD. Prior exposure to diazepam in group 2 after sessions 1-7 conditioned the animals so that a greater release in punished behavior was seen during sessions 8-12 than in the control group (1). In Experiment 2, one group (3) of rats was administered diazepam vehicle after the CSD session for 4 drug test days and another group (4) was injected with 5.6 mg/kg diazepam after the CSD session on these same days. On the next 4 drug test days both groups received diazepam before they performed in the CSD. An ITP was observed in both the control (3) and the drug-conditioned (4) group, although the ITP was less obvious in the conditioned group. After a 28-day period of CSD exposure without vehicle or drug treatments, 5.6 mg/kg diazepam was administered to both groups before the CSD session for an additional 8 drug test days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Comparison of anorexia and motor disruption by cyclazocine and quipazine.

The mixed narcotic agonist-antagonist cyclazocine and the 5-HT agonist quipazine disrupt food-rewarded fixed ratio-40 (FR-40) operant behavior in rats as a dose-dependent decrease in the number of reinforcers obtained and a reciprocal increase in the number of 10-second intervals between responding ("pausing"). This disruption has been shown to result in part from interaction with 5-HT neuronal systems, and may be a consequence of: (1) disruption of cognitive processes, (2) motivational impairment, or (3) motor deficits. To identify which of these components is (are) involved in the disruption of operant responding, female Sprague-Dawley rats were tested for food consumption, spontaneous locomotor activity, or rotarod performance following intraperitoneal injection of cyclazocine, quipazine, or both. Cyclazocine decreased food consumption at doses larger than those required to disrupt operant behavior, while quipazine decreased consumption at doses disruptive to operant responding. Little effect was exerted by either drug on spontaneous locomotor activity, while rotarod performance was disrupted only by very large doses of either drug relative to effects of FR-40 behavior. These data indicate that neither drug appears to disrupt operant behavior by causing gross motor deficits. Thus, cyclazocine may disrupt operant responding by impairing cognition, while quipazine may act through food satiation mechanisms.

Animals↗
PubMed1985

The 5HT2 antagonist pirenperone reverses disruption of FR-40 by hallucinogenic drugs.

Indolealkylamine and phenethylamine hallucinogens disrupted responding maintained under a fixed-ratio 40 (FR-40) schedule of reinforcement. LSD, DMT, mescaline and DOM produced dose-dependent decreases in number of reinforcers and increases in 10-sec periods of non-responding (pause-intervals). The 5HT agonist quipazine, as well as the LSD congener lisuride, altered response patterns in a similar manner. The effects of these drugs were examined after pretreatment with pirenperone, an antagonist with specificity toward the 5HT2 receptor with reference to the 5HT1 receptor. The dose-response curves for the phenethylamine hallucinogens were shifted significantly to the right and to a greater degree than were those for the indolealkylamine hallucinogens. Pirenperone also antagonized the effects of quipazine to a degree similar to that observed with the phenethylamine-type hallucinogens. Pirenperone did not significantly shift the dose-response pattern to lisuride. These data suggest that the behavioral disruption induced by these hallucinogens and quipazine relates at least in part to an effect on 5HT2 receptors, while the effects of lisuride do not involve a significant interaction at the 5HT2 receptor.

Animals↗
PubMed1985

Chronic haloperidol treatment: effects on operant responding and inter-response time.

Three groups (n = 6) of male Sprague-Dawley rats were trained to barpress for food reinforcement on a fixed ratio-40 schedule. Each group then received one of three doses of haloperidol (0.125, 0.25, or 0.5 mg/kg, i.p.) according to the following treatment regimen: Baseline, Presession, Postsession, Presession, Postsession, Baseline, Extinction. Each treatment lasted six days each. Only the Presession and Extinction conditions resulted in a significant decrease in the number of reinforcements earned. The number of inter-response times greater than ten sec was inversely related to the number of reinforcements earned. The fact that chronic presession, but not postsession treatment, significantly decreased the number of reinforcements earned would favor an anhedonia interpretation over one postulating cumulative motor deficits. In any event, prior concurrent experience with the drug effect and the operant behavior appears to be critical to the decrement induced by haloperidol.

Animals↗
PubMed1985

Diazepam-ethanol interaction: initial treatment and combined treatment effects.

Water-deprived female Sprague-Dawley rats were trained in a conditioned suppression of drinking paradigm. Experiment 1 assessed the effects of prior experience with ethanol on the initial treatment deficit of diazepam (1A) and the influence of prior experience with diazepam on the initial treatment effects of ethanol (1B). In Experiment 1A, half the animals received three daily doses of ethanol, while the other half received vehicle for 3 days. All rats then received vehicle followed by 3 days of ethanol treatment. No significant effect of prior experience with ethanol was observed on the diazepam initial treatment deficit. In Experiment 1B, half the animals received vehicle followed by three daily doses of diazepam, while the other half received vehicle. All subjects then received vehicle followed by 3 days of ethanol treatment. No significant effect of prior experience with diazepam was noted on ethanol's initial treatment effects. Experiment 2 assessed the effects of diazepam (0, 1, 2, and 4 mg/kg) and ethanol (0, 0.5, 1 and 2 g/kg) alone and in combination in the conflict test. Diazepam, administered alone, resulted in an antipunishment effect. Ethanol alone did not produce an antipunishment effect. The combination of the two drugs generally decreased both punished and unpunished responding. Further, the CNS depressant effects of these drugs appear to be additive. The qualitative effects of these two drugs are different enough to disallow generalization to each other in a conflict test.

Animals↗
PubMed1984

Behavioral effects of intracerebroventricular administration of LSD, DOM, mescaline or lisuride.

The effects on a fixed ratio-40 (FR-40) operant behavior of intracerebroventricular (ICV) administration of the hallucinogens lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM), mescaline or the non-hallucinogenic LSD-analogue lisuride were compared with intraperitoneal (IP) administration. Infusion of LSD (8.5 to 34 micrograms) into the left lateral ventricle produced a dose-dependent decrease in reinforcers and an increase in 10-sec periods of non-responding (pause intervals). The time-course of LSD showed a shorter latency to onset after ICV than IP administration. The ED50 for doses increasing pause intervals by ICV administration was 15 micrograms. This disruption was greater than that produced by IP administration of equivalent doses of LSD (IP ED50: 19 micrograms). DOM (40 to 120 micrograms) infused into the lateral ventricle also produced a dose-dependent disruption of FR-40 behavior. ICV DOM also showed a rapid onset to peak effects, but a slower offset than LSD, and was 3 times more potent than systemic administration (ED50s: 58 micrograms ICV vs. 153 micrograms IP). Mescaline was much more potent in disrupting FR-40 behavior by the ICV route than by IP administration. The ICV ED50 for doses of mescaline increasing pause intervals was 74 micrograms, in contrast to an ED50 following systemic administration of 2251 micrograms, demonstrating a 30-fold difference in potency. Lisuride administered via the ICV route was no more potent than by IP administration with ED50s of 4 micrograms ICV and 4 micrograms IP. Lower doses of lisuride administered by both routes had a similar effect over time on pause intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
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↗
PubMed1984

Naloxone alters the effects of LSD, DOM and quipazine on operant behavior of rats.

Administration of the indolealkylamine hallucinogen d-lysergic acid diethylamide (LSD), the phenethylamine hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) and the putative 5-hydroxytryptamine (5-HT) agonist quipazine all produced a dose-dependent decrease in fixed ratio (FR-40) response rates and a concomitant increase in the number of 10-second pause intervals. Although naloxone (4.0 mg/kg) had no effect on FR-40 responding per se, the pause-producing effects of LSD and, to a lesser extent, DOM were potentiated by pretreatment with naloxone. The action of quipazine on reinforcers was unaffected by combination with naloxone, while the effect on pause intervals was slightly attenuated by naloxone pretreatment. These data and previous studies suggest that the pause-producing effects of indolealkylamine and phenethylamine hallucinogens reflect their activation of a selective portion of brain 5-HT receptors. The potentiation of these effects by naloxone may relate to a modulation of central 5-HT systems by endogenous opioid mechanisms tending to restore an imbalance in various 5-HT pathways caused by the hallucinogenic 5-HT agonists. The more generalized disruptive effects of quipazine on brain 5-HT systems may be less susceptible to the endogenous opioid modulation or may actually combine with it to induce a greater disruption.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1983

Cyclazocine disruption of operant behavior is antagonized by naloxone and metergoline.

Male Sprague-Dawley rats were trained to press a lever on a fixed ratio-40 (FR-40) schedule for food reinforcement. Doses ranging from 0.5 to 16 mg/kg of the mixed narcotic agonist-antagonist cyclazocine (30-min pretreatment) resulted in a dose-dependent decrease in the number of reinforcements obtained and a reciprocal increase in "pausing" (IRT's greater than 10 sec). A 5-min pretreatment with 4 mg/kg of the narcotic antagonist naloxone attenuated the cyclazocine disruption. The 5-HT antagonist metergoline (1 mg/kg; 180-min pretreatment) also blocked cyclazocine effects to approximately the same degree as did naloxone. However, the shift of the dose response pattern of cyclazocine was not parallel for either antagonist. A greater degree of attenuation of the cyclazocine effects was observed when naloxone (4 mg/kg) and metergoline (0.1 mg/kg) were given together, indicating that cyclazocine disruption may be antagonized by either a narcotic antagonist or a 5-HT antagonist, and that these antagonists may operate synergistically. Thus, the behavioral effects of cyclazocine may relate to both opioid and serotonergic components.

Animals↗
PubMed1983

Tolerance and cross-tolerance to central nervous system depressants after chronic pentobarbital or chronic methaqualone administration.

This study reports on tolerance and cross-tolerance to the rotarod (RR)-disrupting effects of various central nervous system (CNS) depressants. Female rats trained on the RR were fed ground chow containing pentobarbital (PB, 2.0 mg/g chow) or methaqualone (MQ, 1.0 mg/g chow) and were injected twice daily (PB) or daily MQ) with 30 mg/kg IP for 6 days. Control rats received ground chow and saline injections. On day 7 the subjects were tested with various doses of PB, MQ, diazepam (DZ), or ethanol (ET) for disruption of RR performance over the time-course of the drug effect (up to 12 hours). Control animals demonstrated a dose-dependent duration of impairment for all 4 agents. Both groups receiving chronic drug showed a prominent decrease in duration of RR impairment after PB, a less marked decrease after MQ, and even less of a decrease after DZ. However, neither chronic drug group showed an appreciable tolerance to the RR disruption of ET, relative to the control group. Based on the time of 50% recovery (RR performance recovering to 90 seconds or more), both chronic treatments resulted in a significant shift of the dose-response curves for PB, MQ and DZ to the right. Therefore, the degree of tolerance and cross-tolerance in rats chronically treated with PB or MQ was dramatic for PB and MQ, was significant for DZ, but was not demonstrable for ET.

Animals↗
PubMed1983

Blockade of the behavioral effects of lysergic acid diethylamide, 2,5-dimethoxy-4-methylamphetamine, quipazine and lisuride by 5-hydroxytryptamine antagonists.

The effects of lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM), quipazine or lisuride alone and in combination with the 5-hydroxytryptamine antagonist metergoline, pizotifen and cinanserin were studied in rats responding on a fixed-ratio 40 schedule of food presentation. LSD, DOM, quipazine or lisuride produced a similar dose-dependent decrease in the number of food presentations (ED50 values: 81 micrograms/kg, 0.6 mg/kg, 1.6 mg/kg and 31 micrograms/kg, respectively) and a reciprocal increase in the number of pause intervals (IRTs = 10 sec). All three antagonists attenuated the behavioral effects of LSD and DOM for both food presentations and pause intervals. The LSD-response curve for reinforcers was shifted to the greatest degree by pizotifen (1.0 mg/kg), followed by cinanserin (20 mg/kg) and metergoline (1.0 mg/kg). The ED50 values for this effect were 334, 181 and 141 micrograms/kg, respectively. The DOM dose-response pattern for decrease in reinforcers was shifted to the greatest degree by metergoline, followed by pizotifen and cinanserin (ED50 values: 26.5, 3.2 and 1.8 mg/kg, respectively). The effect of quipazine on reinforcers was antagonized by metergoline and pizotifen (ED50 values: greater than 8.0 for both) but not by cinanserin, although all three antagonists attenuated the increase in pause intervals in the same order as they did for DOM. The decrease in reinforcers by lisuride was equally antagonized by metergoline and pizotifen (ED50 values: 58 and 57 micrograms/kg, respectively), whereas cinanserin potentiated the effect of lisuride (ED50: 16 micrograms/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1983

Negative chronotropic and positive inotropic actions of phencyclidine on isolated atrial muscle in guinea pigs and rats.

Chronotropic and inotropic actions of phencyclidine were studied in spontaneously beating right atrial muscle and electrically paced left atrial muscle preparations isolated from guinea-pig or rat hearts. In right atrial muscle preparations, phencyclidine (10-100 microM) decreased the frequency of spontaneous beating. Guinea-pig and rat heart preparations had similar sensitivities to this action of phencyclidine. The negative chronotropic effect was not altered by atropine. A high concentration of naloxone failed to affect the chronotropic effect of phencyclidine in guinea-pig muscle, but significantly reduced the effect in rat heart muscle preparations. Phencyclidine (1-100 microM) caused positive inotropic effects in both guinea-pig and rat heart left atrial muscle electrically stimulated at 1.5 Hz; rat heart preparations had a higher sensitivity to the positive inotropic action of phencyclidine. The positive inotropic effect was reduced by verapamil, nifedipine and relatively high concentrations of diltiazem, but was not affected by propranolol, phentolamine, tripelennamine, atropine or ryanodine, indicating that the effect is not mediated by adrenergic, histaminergic or cholinergic systems or does not involve ryanodine-sensitive calcium pools. Inactivation of the fast sodium channels by partial membrane depolarization, and subsequent restoration of the contraction by raising the extracellular Ca++ concentration, did not abolish the positive inotropic action of phencyclidine. These results suggest that the negative chronotropic effect of phencyclidine is not mediated by a stimulation of the muscarinic receptor. The positive inotropic effects of phencyclidine seem to result from an increase in Ca++ influx through the slow channels of the cardiac cell membrane.

Action Potentials↗
PubMed1982

Lack of central 5-hydroxytryptamine influence on the anticonflict activity of diazepam.

This study examined the effects of various drug treatments (IP injections) proposed to modify central 5-hydroxytryptamine (5-HT) activity on a conditioned suppression of drinking behavior in water-deprived rats. The subjects were trained to drink their daily water requirement during a 10-min session. Intermittent tone periods of 7 s were then introduced, the last 5 s of which the drinking tube was electrified. The animals gradually suppressed tube contacts during the tone to a low constant level within 2 weeks of training. Diazepam increased punished responding dramatically. The 5-HT antagonists methysergide (1 - 18 mg/kg), cyproheptadine (1 - 18 mg/kg), metergoline (0.25 - 2.0 mg/kg) and cinanserin (10 - mg/kg) failed to induce large, reliable increases in punished responding. When a low dose of diazepam was combined with 5-HT antagonists, only one treatment, methysergide at 3 mg/kg, potentiated the anticonflict activity of diazepam. Acute or chronic treatment with PCPA increased behavior suppressed by punishment, but this effect was weak, brief, and poorly related to the depletion of brain 5-HT. LSD (0.3 - 100 microgram/kg) administered 1, 10, or 30 min before the test was ineffective in overcoming suppression by punishment. Mescaline (6 - 30 mg/kg) had no significant effect on punished responding. 5-HTP (18 mg/kg) decreased the number of shocks accepted, but not after pretreating with carbidopa. Pretreatment with carbidopa plus 5-HTP potentiated the anticonflict effect of diazepam. The 5-HT agonist mCPP (0.25 - 2.0 mg/kg) enhanced suppression due to punishment, but only in doses that interfered with unpunished responding. The 5-HT-releasing agent fenfluramine (0.25 - 1.0 mg/kg) did not affect this behavior. Amitriptyline pretreatment in a dose not affecting unpunished behavior (5.6 mg/kg) potentiated the diazepam-induced increase in punished responding. These results are difficult to reconcile with the proposal that suppression of behavior consequent to punishment is related to brain 5-HT activity.

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↗