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Biomedical subjects

E P Schoener

Publications and source records attributed to E P Schoener.

At least 19 recordsLinked to original sources
PubMed2000

Prevalence of attention-deficit/hyperactivity disorder and conduct disorder among substance abusers.

BACKGROUND: This cross-sectional study sought to determine the prevalence of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder among adults admitted to 2 chemical dependency treatment centers. It was hypothesized that ADHD alone or in combination with conduct disorder would be overrepresented in a population of patients with psychoactive substance use disorders. METHOD: Two hundred one participants were selected randomly from 2 chemical dependency treatment centers. Standardized clinical interviews were conducted using the Structured Clinical Interview for DSM-IV, the Addiction Severity Index, and DSM-IV criteria for ADHD. Reliabilities for the diagnostic categories were established using the Cohen kappa, and the subgroups of individuals with and without ADHD and conduct disorder were compared. RESULTS: Forty-eight (24%) of the participants were found to meet DSM-IV criteria for ADHD. The prevalence of ADHD was 28% in men (30/106) and 19% in women (18/95; NS). Seventy-nine participants (39%) met criteria for conduct disorder, and 34 of these individuals also had ADHD. Overall, individuals with ADHD (compared with those without ADHD) were more likely to have had more motor vehicle accidents. Women with ADHD (in comparison with women without ADHD) had a higher number of treatments for alcohol abuse. Individuals with conduct disorder (in comparison with those without conduct disorder) were younger, had a greater number of jobs as adults, and were more likely to repeat a grade in school, have a learning disability, be suspended or expelled from school, have an earlier age at onset of alcohol dependence, and have had a greater number of treatments for drug abuse. They were more likely to have a lifetime history of abuse of and/or dependence on cocaine, stimulants, hallucinogens, and/or cannabis. CONCLUSION: A significant overrepresentation of ADHD exists among inpatients with psychoactive substance use disorders. Over two thirds of those with ADHD in this sample also met criteria for conduct disorder. Our sample had a very large overlap between ADHD and conduct disorder, and the major comorbidities identified here were attributable largely to the presence of conduct disorder. Individuals who manifest conduct disorder and/or ADHD represent a significant proportion of those seeking treatment for psychoactive substance use disorders. They appear to have greater comorbidity and may benefit from a treatment approach that addresses these comorbidities specifically through medical and behavioral therapies.

Adolescent↗
PubMed1998

Interactions of buprenorphine and selective dopamine receptor antagonists in the rat nucleus accumbens.

1. Extracellular recording of spontaneously active nucleus accumbens neurons was employed to characterize interactions of the mixed opioid buprenorphine and selective dopamine receptor antagonists. 2. Buprenorphine caused depression of single-unit activity at all doses tested but evoked facilitation only at low doses. 3. In experiments with the D1 antagonist SCH 23390, buprenorphine-induced depression was consistently blocked, but facilitation was unaffected. 4. Conversely, the D2 antagonist eticlopride blocked buprenorphine-induced facilitation, though it was ineffective against depression.

Animals↗
PubMed1996

Age-dependent decline of attention deficit hyperactivity disorder.

OBJECTIVE: This study was undertaken to assess whether the diagnosis of attention deficit hyperactivity disorder (ADHD) is retained from childhood into adulthood. METHOD: A search of the literature yielded nine prospective studies in which cohorts of children with the disorder were formed and then reexamined 4-16 years later to determine the level of retained ADHD. The resulting data were subjected to nonlinear regression analysis to ascertain the relationship with chronological age. RESULTS: The data followed an exponential decline over time to a high degree of accuracy. CONCLUSIONS: The rate of ADHD in a given age group appears to decline by 50% approximately every 5 years. If a prevalence of ADHD in childhood of 4% is assumed and the exponential decline extrapolated, the estimated rate of adult ADHD ranges from about 0.8% at age 20 to 0.05% at age 40.

Adolescent↗
PubMed1995

Alpha 1-adrenergic receptor antagonist blocks acute cocaine action on the compound action potential of the auditory nerve in the chinchilla.

Acute systemic cocaine injection is known to significantly decrease the compound action potential (CAP) amplitude of the auditory nerve. In an attempt to elucidate the mechanism underlying this phenomenon, the present study investigated the influence of prazosin, an adrenergic alpha 1-receptor antagonist, on the effect of cocaine on the CAP. Amplitude-intensity functions at 1 and 8 kHz were obtained before and after treatment with cocaine (experimental group) or saline (control group) in prazosin pretreated subjects. The characteristic reduction in CAP amplitude after an acute cocaine injection was blocked by 0.05 mg/kg prazosin. When subjects were re-injected with cocaine or saline one h after prazosin, the reduction in CAP amplitude following cocaine injection had recovered.

Adrenergic alpha-Antagonists↗
PubMed1994

Effects of repeated cocaine injections on cochlear function.

The effects of repeated cocaine administration on cochlear function were evaluated by measuring amplitude-intensity and latency-intensity functions of the whole-nerve action potential of the auditory nerve. Whole-nerve action potential input/output functions obtained using tone-pips of 0.5, 1, 2, 4 and 8 kHz in a group of cocaine-treated subjects were compared with those obtained in saline-treated animals. All measurements were made 24 h after the last treatment. Amplitudes of whole-nerve action potentials were enhanced in the cocaine-treated animals compared to the control group. No statistically significant differences in latency-intensity functions were seen after cocaine treatment. The effect of chronic cocaine exposure also was examined on catecholamine innervation in the cochlea using immunohistochemical techniques. The density of adrenergic innervation was reduced in the cocaine-treated animals.

Acoustic Stimulation↗
PubMed1994

Effects of selective dopamine receptor compounds on single, spontaneously-active neostriatal neurons.

1. The effects of selective dopamine receptor compounds on the spontaneous activity of single neostriatal neurons were examined extracellularly. 2. Intravenous administration of quinpirole, the D2 agonist, elicited a dose-dependent depression in discharge rate. 3. Quinpirole-evoked depression was reversed by the D2 antagonist eticlopride, but not the D1 antagonist SCH 23390. 4. The partial D1 agonist, SKF 38393 induced depression and excitation in equal proportion. 5. A dose of 0.25 mg/kg SCH 23390 blocked SKF 38393-induced depression but not excitation. 6. SKF 38393-induced excitation was antagonized by eticlopride and in some cases by a higher dose of SCH 23390.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Effects of prior cocaine exposure on subsequent neuronal responsiveness.

In vivo electrophysiological experiments were conducted to examine the responses of single, spontaneously-active neostriatal neurons to repeated cocaine exposure. The second of two administrations in a 30 min interval, attenuated the magnitude and duration of cocaine-induced depression in discharge rate, and enhanced the same variables for cocaine-evoked excitation. These findings indicate that the responsiveness of striatal neurons to cocaine may vary predictably as a function of previous exposure.

Akathisia, Drug-Induced↗
PubMed1993

Cocaine and dopaminergic actions in rat neostriatum.

Electrophysiological experiments were conducted in vivo to characterize the involvement of dopamine in effects of cocaine at the cellular level. L-DOPA (preceded by carbidopa) evoked excitation and depression equally at 0.25 mg/kg; however, at 0.5 and 1.0 mg/kg depression in the basal rate of discharge predominated. Cocaine evoked similar responses. At 0.25 and 0.5 mg/kg excitation and depression were elicited in about equal proportion, while at 1.0 mg/kg depression was predominant. Cocaine-induced neuronal changes were reversible by haloperidol. In experiments with specific dopamine antagonists, cocaine-induced neuronal depression was blocked with the D1 antagonist, SCH 23390 at a dose of 0.25 mg/kg. The D2 antagonist, eticlopride, did not alter cocaine-induced depression in any specific manner. Excitation, following cocaine, was not altered by intervention with SCH 23390, yet it was blocked with the D2 antagonist eticlopride at a dose of 0.25 mg/kg. The duration of these changes was consistent with the observed duration of the psychotropic actions of cocaine.

Animals↗
PubMed1993

Effects of harmane (1-methyl-beta-carboline) on neurons in the nucleus accumbens of the rat.

Harmane, a beta-carboline alkaloid reported to exert locomotor and psychoactive effects, is found in certain plants and also has been shown to exist in the mammalian brain as an endogenous substance. In this study, the effects of locally perfused harmane were examined on spontaneous neuronal activity in the nucleus accumbens of urethane-anesthetized rats. Extracellular single-unit recording, coupled with push-pull perfusion, enabled the discrimination of specific, dose-related effects of harmane across a wide concentration range. At lower concentrations (10(-9)-10(-11) M), excitation prevailed, while at higher concentrations (10(-8)-10(-6) M) depression was most pronounced. These findings suggest a neuromodulatory role for harmane in the forebrain reward system.

Animals↗
PubMed1990

Cardiorespiratory function is altered by picomole injections of 5'-N-ethylcarboxamidoadenosine into the nucleus tractus solitarius of rats.

A limited occipital craniotomy was conducted on urethane-anesthetized, spontaneously breathing rats to expose the caudal medulla in the region of the obex. Microinjections of 5'-N-ethylcarboxamidoadenosine (NECA), an adenosine analog, were made into the medial region of the caudal nucleus tractus solitarius (NTS) at the level of the caudal tip of the area postrema, an area of the NTS in which there is known to be a functional co-existence of cardiovascular and respiratory-related neuronal elements. Cardiorespiratory responses were subsequently recorded for a 60 min test period. Microinjections of NECA, in the dose range of 0.35-350 pmol per rat, produced significant dose-related reductions in respiratory rate which were accompanied by dose-dependent increases in tidal volume and these pronounced effects on respiration persisted throughout the test period. In contrast, the effects of NECA microinjections on cardiovascular parameters in this region of the NTS were bidirectional and elicited considerably more complex responses during the test period. During the initial period (2-5 min) following injection, NECA elicited significant hypotension (at lower doses) and pressor responses (at higher doses) in addition to significant bradycardia (at lower doses) whereas by the end of the 60 min test period, almost all doses of NECA had resulted in hypertension and tachycardia. Multivariate analysis of variance (MANOVA) and correlation statistics indicated that the effects of NECA on blood pressure during the initial 2-5 min were dose-dependent and unlikely related to depression of respiratory frequency. A further examination of the data by MANOVA indicated that the pharmacological effects of NECA during the 60 min test period exhibited a highly significant and specific dose-dependent and time-related response pattern for the respiratory, but not the cardiovascular, parameters. Taken together, these manifold response patterns suggest that the respiratory effects of NECA may be mediated by different intrinsic mechanisms in the NTS than are the cardiovascular effects of NECA. At the end of the 60 min test period following the administration of NECA, the respiratory rate remained profoundly depressed. In view of previous studies showing that microinjections of cyclic AMP analogs, forskolin, isoproterenol and adenosine into the same NTS sites elicit a similar depression of respiration, the results with NECA in the present study further support the notion that cyclic AMP may serve as a second messenger in NTS respiratory control regions and these respiratory depressant effects may be mediated by a single adenosine receptor subtype.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗
PubMed1988

Respiratory effects of cyclic AMP following injection into the nucleus tractus solitarius of rats.

Rats were anesthetized with urethane and a limited occipital craniotomy was performed to expose the caudal medulla in the region of the obex. Injections were made into sites in the brainstem of spontaneously-breathing rats through glass micropipettes. Tidal volume, respiratory frequency, minute volume, blood pressure and heart rate were recorded before and after the administration of 8-bromoadenosine 3',5'-cyclic monophosphate (Br-cAMP), an analog of cyclic AMP. Injections of Br-cAMP into the ventromedial portion of the caudal nucleus tractus solitarius (NTS) produced dose-related decreases in pulmonary ventilation due to effects on both respiratory frequency, as well as minute volume. In larger doses, Br-cAMP produced periodic apnea and irregular breathing. The respiratory depression was accompanied by transient hypotension and bradycardia. The data indicate that cyclic AMP may function as a second messenger in respiratory control regions in the brainstem.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Cardiovascular effects of microinjections of adenosine analogs into the fourth ventricle of rats.

Rats were implanted with chronic indwelling cannulae into the posterior region of the fourth ventricle. After recovery from surgery, acute experiments on blood pressure were conducted under urethane anesthesia. The blood pressure and heart rate responses following administration of two adenosine analogs, NECA and L-PIA were examined. Microinjections of both analogs produced dose-dependent reductions in blood pressure and heart rate. NECA was approximately 20-fold more potent than L-PIA in reducing blood pressure and depressing heart rate. The cardiovascular effects of both analogs were antagonized by parenteral injections of caffeine. These findings show that microinjections of analogs of adenosine into the fourth ventricle can influence areas of the central nervous system involved in cardiovascular control.

Adenosine↗
PubMed1986

Mechanisms of depressant drug action/interaction.

Whereas the effects of individual psychotropic drugs depend upon drug type, route of administration, dose, and frequency of use, as well as unique subject (patient) variables, the actions achieved by two or more psychotropics taken concurrently are complicated by their influence upon each other. Interactions may be antagonistic, additive, or synergistic and are frequently predictable, given a basic understanding of the kinetic and dynamic characteristics for each drug. This knowledge should enable rational interpretation, therapeutic intervention, and possible prevention of polydrug toxicity. Classically, pharmacodynamic drug interaction is described in terms of common receptor activation or antagonism. This limited view is inadequate in the present context and should be broadened to encompass all of the mechanistic elements that initiate, transduce, and amplify neuronal membrane action. Thus, although psychotropic drugs may compete for a limited number of specific binding sites, as the opiates do, they may also interact through allosteric mechanisms and nonspecific modulation of the receptor environment or subsequent effector cell mechanisms. Drugs in the depressant class often act synergistically in these ways. Through consideration of nonreceptor mediated interaction, we can more fully appreciate the potentiation that occurs between seemingly unrelated substances (e.g., antihistamines and ethanol) and the ability or lack thereof to medically treat such interactions specifically. The pharmacokinetic determinants of drug action provide many opportunities for synergy between psychotropic drugs. Each process is a fertile substrate. Absorption from the gastrointestinal tract is sensitive to drugs that alter peristaltic motility and glandular secretion. Those that inhibit motility tend to delay the rate, if not the extent, of absorption and consequently reduce peak intensity and prolong duration of the psychotropic effect. Serum albumin binding can be a vital point of interaction for drugs with high intrinsic binding affinity (e.g., 98% for methadone); displacement of a small amount of bound drug by a competing substance may increase the free drug concentration severalfold and thereby potentiate its actions(s). Psychotropic drug effects would last for days and even weeks, were it not for the body's ability to synthetically alter drug molecule configuration. This process takes place primarily in the liver where oxidative reactions are frequently catalyzed by the mixed function oxidase system.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Anxiety Agents↗
PubMed1985

Cardiovascular effects of centrally perfused clonidine.

Earlier work has indicated that the systemic cardiovascular actions of clonidine might be mediated by caudal brainstem centers, especially the nucleus of the solitary tract (NTS). This study sought to define the mode of clonidine action on the NTS more explicitly using the technique of push-pull perfusion on urethane-anesthetized rats. The NTS of stereotaxically mounted subjects was unilaterally perfused with an artificial cerebrospinal fluid at 25 microliter/min. Clonidine was added to the medium at concentrations of 5 to 500 microM, without interruption of flow, for test periods of 10 min. Systemic drug actions were expressed in terms of mean arterial pressure (MAP) and heart rate (HR), both of which were recorded continuously throughout the experiment. Decreases occurred in both MAP and HR following clonidine perfusion at all concentrations. However, the dose-effect relationship for the blood pressure response was dependent to some extent on control pressure. When this was considered as a variable, the drug-induced pressure effects were significantly dose-dependent. Control HR values were more stable than pressure and dose-related decreases following clonidine administration were highly significant. The clonidine concentrations investigated here were considerably lower than those previously studied by microinjection. The observed dose-related depression of MAP and HR under basal conditions may be related to specific alpha 2-adrenergic receptor activation of the NTS.

Animals↗
PubMed1984

Neuronal response to dopamine in rat neostriatum. A push-pull perfusion study.

In light of the sustained controversy surrounding the effects of dopamine (DA) in the striatum, this investigation sought to identify the pharmacological effects of locally infused DA on neuronal function. A push-pull perfusion technique of discrete drug application was employed, with single unit extracellular recording, in attempts to establish a clear dose-effect relationship between DA and neuronal activity. Locally perfused DA was found to modulate the discharge rate of striatal neurons over the entire test range (10(-7)-10(-10)M). Varied responses were detected, with 7% of the units exhibiting facilitation and 55% depression; 11% of these displayed biphasic excitation/inhibition. Taking everything into consideration, no strict dose-response relationship was evident for excitation and depression. However, the degree of depression appeared to be directly related to the concentration of DA which was perfused, especially when considered as a function of the initial discharge rate. Upon repeated perfusion of DA, the neuronal responsiveness progressively declined. These observations are consistent with data derived from extracellular, iontophoretic studies on the same neuronal population.

Animals↗
PubMed1979

Cyclic nucleotides in the rat neostriatum: push-pull perfusion studies.

A push-pull perfusion technique was employed for in vivo study of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in the rat caudate nucleus. Addition of dopamine to the perfusion fluid elicited dose-dependent increases of both cAMP and cGMP perfusate concentrations. In separate experiments, it was found that pretreatment of animals with the dopamine antagonist, pimozide, significantly depressed both nucleotide responses to dopamine perfusion over the dose range studied. Mechanistic interpretations of the observations are considered. The push-pull perfusion technique appears to provide an extremely useful means of examining extracellular cyclic nucleotide levels in a discrete brain region, in vivo, under dynamic conditions.

Animals↗
PubMed1977

Accumulation of radioactive cardiac glycosides by various brain regions in relation to the dysrhythmogenic effect.

Ouabain was administered at a loading dose of 3 mug/kg followed by an infusion at a rate of 1 mug/kg-1 min-1 in order to produce severe dysrhythmia in dogs within 60 minutes. Similarly, digitoxin at a loading dose of 9 mug/kg followed by an infusion at a rate of 3 mug kg-1 min-1 was administered to compare its effect with that of ouabain. 2 During the 60 min experimental period, the plasma concentrations gradually rose with the continuous infusion of these drugs. However, in comparison to the 60 min plasma value of 119+/-20 pmol/ml for ouabain and 177+/-68 pmol/ml for digitoxin, the cerebrospinal fluid (CSF) concentrations for these drugs at this time were less than 5 pmol/ml. 3 Upon termination of the experiment at 60 min it was found that kidney, liver, heart, adrenal, and the non-neural tissue in the brain such as pituitary and choroid plexus concentrated ouabain and digitoxin to give high tissue to plasma ratios. However, various neural areas of the brain (cerebellum, mesencephalon, hypothalamus, pons, and medulla) showed no preferential localization or uptake of these two glycosides. 4 Concentration of ouabain and digitoxin by the choroid plexus does not seem to affect the ionic composition of the CSF. 5 It was concluded that sampling the large areas of neural tissue above could provide no evidence for local accumulation of digitalis glycosides that might account for a central nervous system origin of digitalis-induced cardiac arrhythmias.

Animals↗