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At least 703 records · Page 39Linked to original sources
PubMed1994

Increased alcohol intake in low alcohol drinking rats after chronic infusion of the beta-carboline harman into the hippocampus.

Harman (1-methyl-beta-carboline) has been shown to induce volitional drinking of ethyl alcohol in the rat. The purpose of this study was to examine the long-term effect of sustained delivery of harman into the dorsal hippocampus on the subsequent preference for alcohol in the genetically bred low alcohol drinking (LAD) rat. The individual pattern of preference for alcohol was first determined following a standard 3-30% alcohol self-selection test for 10 days. Thereafter, a cerebral cannula for constant infusion was implanted stereotaxically into the dorsal hippocampus. The cannula was attached to an osmotic minipump implanted subcutaneously, which was filled with either an artificial cerebrospinal fluid (CSF) vehicle or harman. Harman was delivered at a rate of 1.0 or 3.0 micrograms/h (i.e., 5.5 or 16.5 nmol/h, respectively) for a period of 14 days. Four days after surgery, the rats underwent a second 3-30% alcohol preference test for 10 days. Both doses of harman induced a threefold increase in the voluntary consumption of alcohol, expressed as g/kg per day. This effect of the beta-carboline seems to be specific for ethanol because its intake by the LAD rats was increased significantly only when concentrations from 11% to 30% were presented. Harman also enhanced the daily intake of food in a dose-dependent manner, but did not affect body weights or the volumes of water and total fluid consumed. These results, thus, demonstrate that the long-term exposure of hippocampal neurons to harman induces a preference for high concentrations of alcohol even in a line of rats lacking such a genetic predisposition.

Alcohol Drinking↗
PubMed1995

The 5-HT4 receptor antagonist, GR113808, reduces ethanol intake in alcohol-preferring rats.

The present study evaluated the effect of the selective 5-HT4 receptor antagonist, GR113808, on ethanol intake in alcohol-preferring rats. Rats were offered 10% ethanol 2 h/day. In the first experiment, rats had food and water ad lib and 10% ethanol was offered from 1800 to 2000 h. In the second experiment, food was freely available, 10% ethanol was offered 2 h/day, from 1800 to 2000 h, and water was offered for 4 h, from 1800 to 2200 h. In both experiments GR113808 was subcutaneously injected at doses of 1, 3, or 10 mg/kg for 4 consecutive days, 5 min before access to ethanol. From the first day of administration, GR113808 significantly reduced the volitional ethanol intake in water sated rats at the three doses tested. In water-deprived rats, it reduced ethanol intake at 3 and 10 mg/kg, without modifying total fluid and food intake. In both experiments the effect of GR113808 remained rather stable during the 4 days of administration. The present findings, showing that the 5-HT4 receptor antagonist, GR113808, selectively reduces ethanol intake in alcohol-preferring rats, suggest that 5-HT4 receptors may play a role in alcohol intake control.

Alcohol Deterrents↗
PubMed1996

Alcohol intake in high alcohol drinking (HAD) rats is suppressed by FG5865, a novel 5-HT1A agonist/5-HT2 antagonist.

Both the 5-HT2 antagonist, FG5606 (amperozide), and the mixed 5-HT1 agonist/5-HT2 antagonist, FG5893, attenuate significantly the volitional intake of alcohol in the cyanamide treated rat. The purpose of the present study was to investigate the effect on alcohol drinking in the selectively bred, high alcohol drinking (HAD) rat of a new and novel 5-HT1A agonist/5-HT2 antagonist, FG5865 (2-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-3-pyridinecarboxy lic acid methyl ester), which shares pharmacological properties with FG5893. Initially, a standard three bottle preference test for water vs. 3% to 30% alcohol solutions was given over 11 days to determine the maximally preferred concentration for each animal. Then water and this solution, which ranged between 9% and 20% with an overall mean absolute intake of 6.3 +/- 0.5 g/kg per day, was offered over three consecutive 4-day test sequences: (1) predrug control; (2) SC injections b.i.d. of either 1.0 mg/kg or 2.5 mg/kg FG5865 or saline control vehicle; and (3) postdrug. Whereas saline failed to alter alcohol consumption of the HAD rats, FG5865 caused a significant dose dependent reduction by as much as 75% in the intakes of alcohol during its administration in terms of both g/kg (p < 0.01) and proportion of alcohol to total fluid intake (p < 0.01). During the administration of 2.5 mg/kg FG5865, alcohol drinking declined from 6.5 +/- 0.3 g/kg to as low as 2.3 +/- 0.2 g/kg per day. Neither the body weight of the HAD animals nor their intake of food was affected by either dose of FG5865. These results uphold the concept that the 5-HT1A and 5-HT2 receptor subtypes in the brain play a part in the aberrant drinking of alcohol of the HAD rat. Because FG5865 influences the activity of serotonergic neurons in the mesolimbic system of the rat, it is envisaged that the drug suppresses alcohol drinking by way of its action on these neurons.

Alcohol Drinking↗
PubMed1986

Not guilty by reason of insanity: a research note.

The question of the insanity defense centers around the moralist-determinist debate. Insanity defense laws are premised on the assumption that individuals choose between right and wrong, and are responsible for that choice. Mental disease, however, can overpower, and thus, not of their own volition, insane persons become out-of-control. Hence, they cannot be held responsible for their behavior or subject to criminal punishment. It is the purpose of the insanity defense, of course, to distinguish between offenders in need of punitive disposition and ones where a medical-custodial disposition is best. The research presented here indicates that defendants who successfully raise the plea of NGRI do not beat the rap. In other words, they do not spend fewer days in confinement via an NGRI plea than had they been convicted and sentenced. Thus, for the reasons of justice, equity, and fairness the insanity defense should be kept intact. The wave of public fear and reaction to the decision in a few highly publicized cases is insufficient grounds for eliminating the plea. Not only is the use of the insanity defense infrequent, but defendants who select it give up important safeguards. Namely, they are unable to plea bargain, are stigmatized as "mad and bad," have no access to probation or parole, and are confined for an indeterminate amount of time. That some would call this leniency we find surprising. And, of course, we should not forget the findings reported here. NGRI acquittees spend more time being locked up. Defendants who successfully raise the NGRI plea are confined until professionals say they are no longer dangerous.(ABSTRACT TRUNCATED AT 250 WORDS)

Colorado↗
PubMed1995

A method for detecting the time course of correlation between single-unit activity and EMG during a behavioral task.

The chance that a change in excitability of one neuron leads to a change in excitability of another is likely to vary within a single volitional act. This temporal variability in functional connectivity is impossible to assess with standard analytical procedures to accurately that measure the correlation between such elements. This reports describes a technique designed to overcome this limitation by expressing a correlation measure calculated repeatedly in short epochs throughout a behavioral trial. The activity of two elements, a motor cortical neuron and a shoulder muscle, that might take place during a drawing task was first simulated so that the correlation could be manipulated. Various correlation algorithms (standard cross-correlation, spike-triggered average, impulse-response function, impulse-response surface) were tested with these data. Spike trains from a monkey's motor cortex and rectified EMG from its posterior deltoid muscle were compared using the same techniques and shown to have a correlation that changed in a characteristic manner throughout a task that required the monkey to draw a sinusoid.

Algorithms↗
PubMed1990

Psychometric deviance in offspring at risk for schizophrenia: I. Initial delineation of a distinct subgroup.

Psychometric signs from the Minnesota Multiphasic Personality Inventory (MMPI), which measure substantive disturbances in thinking, social relatedness, volition, and affective expressivity, were evaluated as possible indicators of transmissible liability specific to schizophrenia. Children of three criterion groups in the New York High-Risk Project--offspring at high risk (HR) for schizophrenia, psychiatric comparison (PC) offspring at risk for affective disorders, and normal comparison (NC) offspring not at augmented risk for psychiatric morbidity--were tested before the expression of schizophrenic psychopathology, when the subjects ranged in age from 13 to 26 years. The rate of psychometric deviance in the HR group (23%) was significantly higher than that in either the PC (7%) or NC (2%) groups, and profile analyses showed that the HR subgroup could be delineated by qualitative distinctions in personality functioning. Our results support the utility of MMPI indicators in etiologic investigations of schizophrenia.

Adolescent↗
PubMed1990

Development of an ability to maintain verbally instructed central gaze fixation studied in 8- to 10-year-old children.

Development of an ability to maintain verbally instructed central gaze fixation was studied in 8-, 9- and 10-year-old boys. The stability of central gaze fixation was tested by the sudden appearance of a novel, peripheral stimulus triggering reflexive saccade. In Experiment I, the ability to maintain verbally instructed central gaze fixation upon nonsense geometrical pattern was found to be equal in 8 and 9 years of life. This ability increased markedly between 9 and 10 years of age. Gaze fixation upon gradually appearing shapes during a TV-like game reducing volitional effort of subject was, however, equal in all age groups. Concentration of attention upon central stimulus as reflected by saccade latency (Experiment I) and P3-N3 amplitude of evoked potentials to peripheral flashes (Experiment II) was equal in both tasks in 8-year-olds. In contrast, higher concentration of attention upon meaningful central stimulus presented during the TV-like game was found in 9- as well as in 10-year-old boys. Developmental changes of the ability to maintain verbally instructed central gaze fixation might be related to the late structural maturation of frontal cortex.

Attention↗
PubMedDate not supplied

Kinematics of arm movements in elderly humans.

Changes in the kinematics of arm movements with age were studied. "Young" (aged 21-23) and "elderly" (aged 68-95) subjects performed a visually guided, step tracking task. Each subject performed movements of eight different amplitudes (10-80 deg) at two volitionally determined speeds ("own speed," "fast and accurate"). Movement durations and maximum velocities were similar for both groups and increased with movement amplitude under all conditions. The young subjects made movements in which approximately the same length of time was spent in accelerating as in decelerating the movement. In contrast, movements by the elderly subjects were temporally asymmetrical, the deceleration phase being longer than the acceleration phase. The ratio of maximum to average velocities (Vm/Vav) was markedly different between the young and elderly subjects, particularly in the smaller amplitude movements (less than 40 deg). Values of this parameter ranged from 1.5 to 6 in the elderly subjects. Movements made by the elderly subjects were more variable than those of the young subjects, particularly so at smaller amplitudes. Variability was most apparent in the deceleratory phase of movement where the elderly subjects often showed hypermetria. Some elderly subjects also showed movement decomposition, the movements being made as a series of discrete submovements. Thus, the elderly subjects displayed some of the characteristics classically described as arising from cerebellar dysfunction.

Adult↗
PubMed1987

Integration of posture and locomotion in acute decerebrate cats and in awake, freely moving cats.

For the past 10 years, our group has been engaged in the study of posture and locomotion in decerebrate cats and in freely moving awake cats. Our initial objective was to analyse the neuronal mechanisms of locomotion from a viewpoint of "postural control". Therefore, in this review, I have focussed my attention on two major control aspects of the brain stem; one related to the interaction of posture and locomotion; and the other to initiation of locomotion. It is apparent that elucidation of the second aspect is feasible. In Fig. 15, I have summarized all the neuronal structures that have been functionally identified as being actively involved in the regulation of posture and locomotion. Obviously, contribution of the cerebello-cerebral pathways and the basal ganglia to both the postural and to the locomotor control cannot be elucidated in decerebrate preparations (Fig. 15A). These contributions can, to a certain degree, be elucidated in intact awake cats (Fig. 15B). Although it is difficult to directly compare the results obtained in the decerebrate cats with those obtained in intact cats, it has been encouraging that the selective activation of certain neuronal structures within the brain stem allowed us to evoke comparable postural and locomotor changes in both groups of preparations. It can be expected that the knowledge obtained from studies of the cerebello-cerebral pathways and of the basal ganglia, together with those that can be further obtained from studies of the brain stem, should result in the elucidation of the two major control aspects of the brain stem described above. In this sense, both the models of the decerebrate locomotor preparation and the freely moving, awake cat seem to provide an unique opportunity to study the nature and the sources of command signals that set the postural and the locomotor synergies into a single functional synergy, and even to approach elucidation of the intriguing question as to how and where volitional control signals for initiating and/or halting locomotion are organized. More than 70 years have passed since the pioneer studies by Sherrington (1906) and by Graham Brown (1911, 1914) on postural control and on locomotion, as exemplified by "decerebrate reflex standing, and stepping" and the "central rhythmic generator" relating to locomotion. Based on these discoveries, Shik, Severin and Orlovsky (1966) have made a splendid breakthrough in a wide area of investigation relating to locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Abnormalities in postural reflexes and voluntarily induced automatic movements in Parkinson patients.

Postural abnormalities were systematically studied in 41 Parkinson patients in relation with the other Parkinson symptomatology. Evidence was collected that kinetic postural mechanisms, including turning in recumbant position, rising from the floor and walking, to be considered as volitional automatic movements, reacted differently on Levodopa therapy compared with static postural reflexes and the classical Parkinson symptoms. This suggests that the neuro-biochemical substrate of these postural movements may involve other than dopaminergic pathways as well.

Basal Ganglia↗
PubMed1993

Respiration-related activity in the biceps brachii muscle after intercostal-musculocutaneous nerve transfer.

Needle EMG and polygraphic recordings of respiration and biceps activity were obtained in 7 patients who had undergone intercostal to musculocutaneous nerve transfer because of severe traumatic injury to the brachial plexus. EMG activity during expiration and inspiration was assessed during quiet breathing, deep breathing, and during sustained inspiration and expiration, and compared to the clinical strength of the biceps muscle. Biceps activity was consistently found during both expiration and inspiration, and in either case separately related to the flexion force levels. Initially this relationship appeared equally strong for both phases. With time, control over flexion changes from a completely respiratory-driven control to a conscious volitional control; however, involuntary effects of respiration always remained present in polygraphic recordings. Theoretical explanations for the change in control are put forward.

Adolescent↗
PubMed1990

Breakthrough pain: definition, prevalence and characteristics.

In the cancer population, the term breakthrough pain typically refers to a transitory flare of pain in the setting of chronic pain managed with opioid drugs. The prevalence and characteristics of this phenomenon have not been defined, and its impact on patient care is unknown. We developed operational definitions for breakthrough pain and its major characteristics, and applied these in a prospective survey of patients with cancer pain. Data were collected during a 3 month period from consecutive patients who reported moderate pain or less for more than 12 h daily and stable opioid dosing for a minimum of 2 consecutive days. Of 63 patients surveyed, 41 (64%) reported breakthrough pain, transient flares of severe or excruciating pain. Fifty-one different pains were described (median 4 pains/day; range 1-3600). Pain characteristics were extremely varied. Twenty-two (43%) pains were paroxysmal in onset; the remainder were more gradual. The duration varied from seconds to hours (median/range: 30 min/1-240 min), and 21 (41%) were both paroxysmal and brief (lancinating pain). Fifteen (29%) of the pains were related to the fixed opioid dose, occurring solely at the end of the dosing interval. Twenty-eight (55%) of the pains were precipitated; of these, 22 were caused by an action of the patient (incident pain), and 6 were associated with a non-volitional precipitant, such as flatulence. The pathophysiology of the pain was believed to be somatic in 17 (33%), visceral in 10 (20%), neuropathic in 14 (27%), and mixed in 10 (20%). Pain was related to the tumor in 42 (82%), the effects of therapy in 7 (14%), and neither in 2 (4%). Diverse interventions were employed to manage these pains, with variable efficacy. These data clarify the spectrum of breakthrough pains and indicate their importance in cancer pain management.

Humans↗
PubMed1993

Transfer of innervated latissimus dorsi free musculocutaneous flap for the restoration of finger flexion.

Transfer of functioning free muscle for the restoration of finger flexion is an uncommon procedure. We present our experience with five patients with severe forearm injuries in whom a latissimus dorsi musculocutaneous free tissue transfer was performed in an attempt to provide soft tissue coverage and active digital flexion. Four patients had active finger flexion with volitional control of the transferred muscle between the tenth and the fifteenth weeks. On average, active flexion lags were 2.0 cm in the index finger, 2.1 cm in the long finger, 2.3 cm in the ring finger, and 1.4 cm in the small finger. Although preoperative grip strength was doubled, postoperative strength was still only about 31% of that on the opposite side. All patients required at least one tenomyolysis or revision tenorrhaphy before the best clinical outcome was achieved.

Adolescent↗
PubMed1991

Addiction to and dependence on benzodiazepines. Diagnostic confusion in clinical practice and research studies.

Considerable confusion continues to surround basic concepts for abuse, addiction, tolerance, and dependence. Clinicians may be making decisions about prescribing these medications without clear definitions and distinctions. The terms are not equivalent in meaning and should not be used interchangeably in clinical application. Moreover, they may occur together or independently and are not etiologically related. Abuse is improper use outside the standard norms. Abuse implies a violation component and a control over the use of the drug. Addiction is a preoccupation with the acquisition and compulsive use of and a pattern of relapse to drugs is spite of adverse consequences. Pervasive to the criteria is a loss of control over drug use and a lack of volitional component in the drug use. In spite of problems in definitions, studies have clearly shown that abuse, addiction, tolerance, and dependence develop commonly in benzodiazepine use.

Adult↗
PubMedDate not supplied

Cyanamide given ICV or systemically to the rat alters subsequent alcohol drinking.

Cyanamide or disulfiram serves to suppress volitional intake of alcohol presumably because of the toxic build-up of acetaldehyde dehydrogenase (AIDH). However, the presence of acetaldehyde systemically favors the in vivo synthesis of addictive-like metabolites in the brain which in turn enhance alcohol drinking. The purpose of this investigation, therefore, was to determine whether cyanamide administered to the rat, which did not have access to alcohol during treatment, would nevertheless affect the subsequent preference for alcohol. In the first experiment, cannulae were implanted bilaterally above the cerebral ventricle of 33 adult male Sprague-Dawley rats so that an artificial CSF or a solution of cyanamide could be infused intracerebroventricularly (ICV). Following post-operative recovery, each rat was tested for its alcohol preference by offering it water and a solution of ethyl alcohol which was increased over 8 days from 3-20%. After a single test concentration of alcohol (range of 5-9%) was selected for each individual animal presented with water over a 5-day interval, cyanamide was infused in a volume of 2.5 microliters per side three times daily for 4 days in one of the following total doses: 0.03, 0.1, 0.3, 0.5 or 1.0 mg. A second five-day preference test was run, and 6 weeks following cyanamide infusions a final 3-20% alcohol preference screen was run over 8 days. The results showed that a long-term, dose-dependent increase or decrease in alcohol intake occurred in those rats reactive to the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMedDate not supplied

Enkephalinase inhibition: regulation of ethanol intake in genetically predisposed mice.

This is the first report of alteration in alcohol intake in mice with a genetic predisposition to alcohol preference and known to have innate brain enkephalin deficiencies. We have been able to significantly attenuate both volitional and forced ethanol intake respectively by acute and chronic treatment with hydrocinnamic acid and D-phenylalanine, known carboxypeptidase (enkephalinase) inhibitors. Since these agents, through their enkephalinase inhibitory activity, raise brain enkephalin levels, we propose that excessive alcohol intake can be regulated by alteration of endogenous brain opioid peptides.

Alcoholism↗
PubMedDate not supplied

Irreversible suppression of alcohol drinking in cyanamide-treated rats after sustained delivery of the 5-HT2 antagonist amperozide.

The purpose of this study was to evaluate the long-term effect of sustained treatment with amperozide, which has been shown to attenuate the volitional drinking of ethyl alcohol in the rat without side effects. Preference for alcohol first was induced pharmacologically in Sprague-Dawley rats by the inhibitor of aldehyde dehydrogenase, cyanamide, administered in a dose of 10 mg/kg twice daily for 3 days. Then following a standard preference test, each rat was offered water and its maximally preferred concentration of alcohol which ranged from 7% to 15%. Following a 4-day pre-drug test, saline control vehicle or amperozide was administered for 7 days by an osmotic minipump implanted in the intrascapular space. A single dose of 208 micrograms/kg/h (i.e., 5.0 mg/kg/day) was selected on the basis of a prior dose response study of amperozide. During the interval of sustained release of amperozide, the consumption of alcohol declined significantly in terms of both absolute g/kg intake and proportion of alcohol to water. When the preference of the rats was retested at 4, 30, 70, 110, and 140 day intervals after the pump had exhausted amperozide, the absolute g/kg consumption of alcohol continued to decline significantly. Unlike other drugs, amperozide did not produce any side effects, particularly on the intake of food or water or on body weight, which suggests a pharmacological specificity of its action.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMedDate not supplied

New drugs for the treatment of experimental alcoholism.

This article presents a current overview of the efforts to suppress pharmacologically the craving, dependence, or other factors associated with the self-selection of alcohol in an experimental animal. The contemporary status of the pharmacotherapy of experimental alcoholism similarly is described for different animal models of alcohol drinking. An evaluation is presented of several classes of drug for their efficacy in ameliorating the volitional ingestion of alcohol in the presence of an alternative fluid. Currently, two main experimental animal models of alcoholism are being used in this endeavor: (a) genetic lines or substrains of high alcohol preferring or high drinking rats; and (b) strains of nondrinking or low alcohol preferring rats which are induced chemically to prefer alcohol. Because of technical, methodological, and other issues surrounding the procedures used to assess the efficacy of a drug in reducing alcohol intake, several of the newer findings remain controversial. For example, serious side effects on the intake of food, caloric regulation, motor activity, or other functions would preclude the clinical utility of the drug. However, several drugs which affect monoaminergic neurons as well as opioid systems in the brain now seem to offer promise as agents which do possess clinical benefits. Two of these drugs, FG5606 (amperozide) and FG 5893 are essentially "antialcoholic" or anticraving and are without any significant side effects on cerebral mechanisms responsible for hunger, caloric intake, motor activity, or other physiological process. Amperozide, a 5-HT2 receptor antagonist with dopamine releasing properties, is particularly notable because of its irreversible nature in attenuating alcohol preference for months after its administration. It is concluded that future pharmacological research on presently available and newly developed compounds will provide exciting opportunities to the clinician who can utilize a particular drug as an adjunctive tool in the therapeutic treatment of the alcoholic individual.

Alcoholism↗