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Biomedical subjects

R E Meyer

Publications and source records attributed to R E Meyer.

At least 19 recordsLinked to original sources

Opiates, catecholamines, behavior, and mood.

Indirect evidence has linked opioid reinforcement with changes in noradrenergic metabolism secondary to drug administration. Methodological precedents for biobehavioral correlations in depressive illness have suggested an important association between changes in mood and biogenic amine excretion patterns in the urines of patients during depression and recovery. This paper presents preliminary data on the possible relationship between changes in catecholamine excretion that were observed and the changes in behavior, mood, psychiatric status, and cardiorespiratory physiology secondary to heroin administration and methadone-assisted withdrawal. This study focuses on the urinary excretion of MHPG, since an appreciable fraction of this metabolite is probably derived from norepinephrine originating in the brain. The subjective changes in mood associated with heroin use, the decrease in respiratory rate, and the behavioral and mental status effects associated with opiate intoxication were observed only in the individuals whose MHPG excretion increased during the period of opiate administration.

Adult

Narcotic blockade, length of addiction, and persistence of intravenous morphine self-administration in rats.

Four groups of rats differing in the number of periods of prior exposure to morphine sulphate in the i.v. self-administration paradigm were studied under conditions of narcotic blockade. Three groups of subjects also differing in the amount of prior exposure to morphine sulphate were studied under saline conditions. At effective blocking doses of naloxone, opioid-seeking behavior was eliminated in relatively drug naive animals, whereas the persistence of secondary reinforcers in rats with longer addiction histories served to maintain opioid consumption in the presence of adequate pharmacological blockade. Data from saline-treated animals were very similar to data obtained in naloxone-treated animals. The authors conclude that at adequate blocking doses of narcotic antagonist the length of addiction appears to be the best predictor of opioid consumption.

Animals

Performance differences between addicts and non-addicts.

Methadone addicts and non-addict controls were tested before and after receiving up to 10 mg of methadone on simple visual reaction time tests and on a vigilance type visual attention test. Addicts were faster than controls on pre-drug testing, although there were no pre-drug differences between groups on the attention task. Addicts maintained faster reaction times than controls even when money was offered as an incentive for speed. Additional methadone did not affect addict performance on any of the tasks. Methadone slowed control reaction times in a dose-related fashion. No significant attention decrements were seen after methadone in controls. Visual reaction time differences between addicts and controls cannot be attributed to group differences in motivation or ability to attend. Slowing of reaction time with acute dose of methadone in controls cannot be attributed to the effect of the drug on attention. An hypothesized drug-induced decrease in visual sensitivity with acute dose in controls and a drug-induced increase in visual sensitivity with chronic dose in addicts can account for the presented data.

Adult

Catecholamine metabolism during heroin use.

The authors examined urinary levels of catecholamines and metabolites during a 10-day period of heroin use in 9 subjects. Catecholamine and metabolite excretion increased over baseline values on the first day of heroin use, but markedly different patterns of change emerged later. In contrast to the significant increase in normetanephrine and decrease in metanephrine excretion in all 9 subjects during heroin use, only 4 subjects showed an increase in 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion. Moreover, it appeared that the increase in MHPG excretion in this subgroup began on the day before heroin administration, which suggests the possibility of an anticipatory or conditioned response.

Catecholamines

Subjects' rights, freedom of inquiry, and the future of research in the addictions.

Since the recent passage of regulations concerning subjects' rights and freedom on inquiry, opposition by the public and others to some areas of research in the addictions has prevented its implementation or continuation. Research investigators in the biomedical and behavioral sciences have been placed in the position of defending their work in an adversary climate. The author points out the importance of transmitting to the public, the scientific community, and legislators the investigators' concern that "subjects' rights" not be viewed only in a legalistic context, but also in the context of not harming the patient.

Advisory Committees

Morphine-based secondary reinforcement: effects of different doses of naloxone.

The effects of different doses of naloxone on morphine-based secondary reinforcement were studied in rats. On the first day a neutral stimulus (buzzer) was repeatedly paired with intravenous morphine infusions. Drug treatments consisted of Low, Medium, or High Naloxone doses, or No Naloxone. The next day the ability of the buzzer and saline infusion to support lever pressing was tested. High Naloxone blocked, and Low Naloxone partially blocked this morphine-based secondary reinforcement. Subjects in the Medium Naloxone group demonstrated an apparent avoidance of the lever, suggesting that the morphine infusions were aversive at this dosage level of naloxone. The secondary reinforcement tests reliably predicted behavior on a subsequent test for acquisition of morphine-seeking behavior.

Animals

Narcotic blockade, length of addiction and persistence of etonitazene consumption in rats.

Rats were given daily trials to determine relative preference for an opiate (etonitazene, ETZ) or for water. Animals with a greater history of previous drug exposure developed ETZ preferences more rapidly than did relatively drug-naive animals. Pretreatment with adequate blocking doses of naloxone reduced drug intake to near zero in most subjects. However, animals with the greatest history of prior addiction continued to drink large quantities of ETZ, despite pretreatment with relatively large doses of naloxone. These results can be explained by assuming that stimuli associated with the reinforcing properties of the opioid solution become strong conditioned reinforcers, capable of maintaining responding for long periods of time despite blockade of the reinforcement properties of the drug.

Analgesics, Opioid

Behavioral and social effects of heroin self-administration and withdrawal.

Behavioral and social reactions to intravenously administered heroin were studied during a 33-day experimental addiction cycle. Three groups of four subject volunteers were allowed to self-administer heroin for a ten-day period as part of a longer study of oplate antagonists. Data relevant to sleep patterns, energy expenditure, social interaction, and other observable behaviors were collected during hourly observations. Comparison of behavioral differences before and after drug administration indicated few significant acute reactions. Reactions to long-term heroin self-administration were most pronounced in the areas of sleep behavior and social interaction. Subjects tended to sleep less, especially during the initial period of acquisition, and to withdraw more from social contact. No changes were noted in energy expenditure during waking hours. The results were interpreted in terms of physiological tolerance, central nervous system arousal, and sleep deprivation.

Adult

A behavioral paradigm for the evaluation of narcotic antagonists.

We have developed an experimental paradigm for the behavioral evaluation of narcotic antagonists. The study specifically examined the heroin-seeking behavior of hard-core narcotic addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. A long-term follow-up program in the community, with aftercare services, was utilized to determine the relationship between behavior observed on the research ward and behavior that occurred in the community. While preliminary one-month follow-up data offered some cause for an optimistic view of narcotic antagonist treatment, behavioral data observed on the research ward raised serious doubts about the possibility of extinguishing heroin self-administration with antagonists. The behavioral data were not consistent with laboratory descriptions of extinction. Rather, the data suggested that narcotic antagonist programs should emphasize the development of contingencies for the reinforcement of narcotic antagonist self-administration to ensure an opiate-free state, instead of focusing on an extinction approach.

Adult

Psychopathology and mood during heroin use: acute vs chronic effects.

In the context of evaluating the effects of a narcotic antagonist on opiate acquisition, 14 detoxified addicts self-administered increasing doses of unblocked heroin intravenously over a ten-day period. Early in the addiction cycle, subjects experienced tension relief and euphoria but this was followed shortly by a shift in the direction of increasing dysphoria and psychopathology. Nonetheless, individual injections of the drug continued to induce brief episodes of positive mood, an effect enhanced by frequent injection. Heroin self-administration was sharply reduced when subjects were blocked with naltrexone, a narcotic antagonist, and the negative effects observed during unblocked drug use were not observed.

Acute Disease

Analysis and modification of opiate reinforcement.

The authors describe a research protocol for the evaluation of narcotic antagonists which examines the heroin-seeking behavior of hard-core heroin addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. This paper serves as an introduction to a series of papers which follow dealing with behavioral, psychiatric, and aftercare results. It describes detailed methods and preliminary results for the first 21 subjects admitted to the study. More specific results are reported in the papers that follow.

Adult

Opiate antagonists and the modification of heroin self-administration behavior in man: an experimental study.

The heroin self-administration behavior of 8 inpatient heroin addicts was examined for 10 days under blocked (i.e., following ingestion of narcotic antagonists--naloxone or naltrexone) and unblocked (no antagonist) conditions. In the unblocked state, subjects injected all the available heroin, but they ceased heroin use almost completely following antagonist administration. Possible explanations for these results are discussed along with their implications for treatment.

Adult

Psychopathology, craving, and mood during heroin acquisition: an experimental study.

Six detoxified addict volunteers were allowed to self-administer intravenous heroin on an essentially self-determined schedule. Two periods of heroin acquisition were compared: an unmodified cycle in which patients could become intoxicated and a later cycle in which the effects of heroin were blocked with a narcotic antagonist. In the unblocked condition, patients initially experienced an increase in positive mood, but with chronic administration there was a significant rise in psychopathology and the development of a generalized dysphoric state. Similar changes did not occur when the same patients took heroin while blocked with a narcotic antagonist. Drug craving rose dramatically when "unblocked" heroin was available, but gradually fell during methadone detoxification. Following treatment with a narcotic antagonist, the presence of heroin failed to elicit any sustained rise in craving and drug taking was dramatically reduced.

Adult