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Biomedical subjects

D R Meyer

Publications and source records attributed to D R Meyer.

At least 109 records · Page 6Linked to original sources
PubMed1978

Clonidine antagonizes naloxone-induced suppression of conditioned behavior and body weight loss in morphine-dependent rats.

Clonidine's action on naloxone (Nx)-induced suppression of fixed-ratio (FR15) responding and body weight loss was studied in morphine (M)-dependent rats. Clonidine (10--70 microgram/kg IP) injected 30 min prior to the behavioral session resulted in a dose-related suppression of operant behavior in M-naive animals. A small, but significant decrease (3--5%) in body weight was also observed at the higher doses of clonidine. More than twice as much weight loss, associated with diarrhea, was obtained when Nx (5.0 mg/kg IP) was administered to M-dependent animals. When clonidine (10--50 microgram/kg IP) was administered prior to Nx, in M-dependent animals, the withdrawal-induced disruption of operant responding was significantly attenuated. Concurrent weight loss, which was significantly antagonized by 1 microgram clonidine/kg, was decreased by as much as 40 percent. The degree of amelioration of withdrawal that was observed appeared to be inversely related to the dose of clonidine. The optimal dose was 10 microgram/kg, which by itself was only partially behaviorally active. At higher doses, clonidine's blocking properties were less apparent as a result of its own potent behavioral suppressant and diuretic effects which masked its capacity to attenuate withdrawal. The data are discussed in relation to the application of operant technics for assessing drug treatment(s) designed to alter the severity of narcotic withdrawal.

Animals↗
PubMed1977

Tolerance and dependence after chronic administration of clonidine to the rat.

Acute administration of clonidine (10-70 microgram/kg, IP) disrupted operant behavior maintained by a fixed ratio schedule of reinforcement [1]. When chronically administered (100 microgram/kg, IP and 3 microgram/ml in drinking water) tolerance to the behavioral depressant effect developed within a few days and was complete by 14 days. Abrupt termination of drug treatment in tolerant rats resulted in an abstinence reaction which was characterized by suppression of operant performance for as long as one week. These results demonstrated the development of tolerance to and dependence on clonidine in rats. These behavioral observations in rats may be related to rebound hypertension and irritability of patients given this alpha-adrenergic agonist for treatment of hypertension.

Animals↗
PubMed1977

An inexpensive microphotometer system for measuring silver grain densities in autoradiographs.

An inexpensive microphotometric system is described which will facilitate reading grain-dense areas in autoradiographic material. It is reliable, easy to operate and adaptable to most light microscopes with a dark field condenser. In addition to the microscope, the components include a photodiode, an operational amplifier and a digital mV meter. Data are presented to demonstrate the sensitivity of the system and to illustrate the differential variability between the microphotometer and the counting of grains by eye.

Animals↗
PubMed1976

Effects of successive unilateral ablations of principalis cortex upon performances of delayed alternation and delayed response by monkeys.

Monkeys were trained on delayed alternation (DA), and were then subjected to serial unilateral or simultaneous bilateral ablations of the banks of the sulcus principalis of each frontal lobe. When subjects with unilateral lesions were retrained on DA, their performances were intermediate to those of normal and bilateral animals. This interoperative training failed to protect the serially operated monkeys from losses of DA following their second-stage ablations, for they then performed as poorly as one-stage subjects and subjects prepared with serial ablations that were not given practice on the task between the two operations. Additional postoperative tests of delayed responding (DR) showed that both serially and simultaneously ablated subjects also had severe impairments of performance of DR. This result confirmed, in principle, a finding that monkeys with large unilateral ablations, if reoperated after many months for the removal of the contralateral dorsolateral perfrontal cortex, will thereafter exhibit DR deficits that are both severe and endure for a period of years. It contrasted sharply with a recent observation that DR is retained by monkeys subjected to two-stage symmetrical ablations of the principalis cortex, which suggests that recoveries of frontal-lobe functions are powerfully affected by the orders in which serial extirpations are performed.

Animals↗
PubMed1976

A comparison of withdrawal in rats implanted with different types of morphine pellets.

Time course and duration and physical dependence was investigated in rats implanted subcutaneously with 3 different types of morphine (M) pellets. Each was formulated according to the method of Gibson and Tingstand [8], but differed in surface area and hardness. Animals were maintained for 19 days after implantation and physical dependence was assessed every other day. Severity of naloxone (Nx)-induced withdrawal was quantified by the use of a composite symptom score and weight loss. Withdrawal severity was greatest following implantation of a pellet (Type C) of large surface area and low hardness rating, and least following implantation of a pellet (Type A) of small surface area and high hardness rating. Abstinence severity which resulted from implantation of a pellet (Type B) of moderate surface area and low hardness rating was intermediate. When 2 pellets were implanted the difference between Type C and B was amplified. It was concluded that formulation per se was not sufficient for specifying M pellet characteristics.

Animals↗
PubMed1976

Bis-basic-substituted polycyclic aromatic compounds. A new class of antiviral agents. 7. Bisalkamine esters of 9-oxoxanthene-2,7-dicarboxylic acid, 3,6-bis-basic ethers of xanthen-9-one, and 2,7-bis(aminoacyl)xanthen-9-ones-xanthenes, and -thioxanthenes.

3,6-Bis[2-(dimethylamino)ethoxy]-9H-xanthen-9-one dihydrochloride (4, RMI 10874DA) and 1,1'-(9H-xanthene 2,7-diyl)bis[2-(dimethylamino)ethanone] dihydrochloride (16, RMI 11513DA) were found to prolong survival of mice infected with lethal challenges of encephalomyocarditis (EMC) virus. They were effective by oral as well as subcutaneous administration and showed broad-spectrum antiviral activity. They were selected for preclinical evaluation from the five series of compounds named in the title that were synthesized in analogy to tilorone and related fluorenone derivatives, described earlier. In addition to 4 and 16, compounds 11, 12, 17, and 18 showed high antiviral activity on oral as well as subcutaneous administration. High antiviral activity on subcutaneous admistration was found in the bisalkamine esters 1,2, and 14, the bis(aminoacyl)xanthenes 23 and 26, the bis(aminoalkylene)xanthene 31, the bis(aminoacyl)thioxanthenes 34-40, and the bis-basic ethers of 9-benzylide-nexanthenes 41 and 42. Structure-activity relationships showed a decrease of oral activity with increased length of side chains and increased molecular weight of dialkylamino substituents of 3,6-bis-basic ethers of xanthen-9-one and of 2,7-bis(aminoacyl)xanthenes and-xanthen-9-ones. At least one carbonyl or alkenyl function in conjugation to the xanthene nucleus either at the 9 position of the nucleus or in the side chains is required for high antiviral activity.

Administration, Oral↗
PubMed1972

Some features of the dorsolateral frontal and inferotemporal syndromes in monkeys.

Our frontal- and temporal-lobe experiments to date support the following conclusions. Anterior temporal or inferotemporal lesions affect object learning set retention, and older work dealing with this task has indicated that temporal ablations, at the very least, retard initial acquisition of the set. Inferotemporal monkeys may lose object sets and yet have no deficits in either the learning or short-term retention of single visual habits. Their well-known impairments in visual pattern learning are products of background-cue learning which become most marked in test situations which bias their responses to these cues. Their pattern-learning deficit is an accentuation of a normal characteristic of the monkey, and implies no profound qualitative alteration of the way that they perceive stimuli. Our work that has dealt with frontal preparations indicates that Jacobsen's effect can be produced either by proactive interference or by difficulties in attending. The latter are probably compensable if lesions are produced in very early infancy, but data from experiments with cats has suggested that perseverative interferences are not. Perseverative tendencies can be suppressed with practice in discrimination learning situations, but the tendencies can then be fully reinstated by relatively minor distractions. Frontal-lobe lesions have almost no effects upon object learning set formation, nor do they have important effects upon a monkey's short-term retention of a habit.

Animals↗