bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditioned taste aversions as a behavioral baseline for drug discrimination learning: Assessment with the dipsogenic compound pentobarbital
Authors: Riley Anthony L. , Jeffreys Ronald D. , Pournaghash Said , Titley Tracey L. , Kufera Angela M. 
Published: January 2005

AbstractAnimals injected with pentobarbital prior to the presentation of a saccharin‐LiCl pairing and its vehicle prior to saccharin alone rapidly acquired the drug discrimination, avoiding saccharin following the administration of pentobarbital and consuming saccharin in its absence. That drug discrimination was acquired within the taste aversion design even though the stimulus drug itself (i.e., pentobarbital) produced significant increases in consumption in nonconditioned control subjects suggests that the dipsogenic properties of a compound are not necessarily a problem for the assessment of drug discrimination learning within the aversion procedure. The present data, along with prior reports on the effectiveness of the taste aversion design with the stimulus drugs phencyclidine and naloxone, indicate that the conditioned taste aversion procedure may be effective as a general method in the assessment of drug discrimination learning.
Pavlovian‐conditioned changes in body temperature induced by alcohol and morphine
Authors: Cunningham Christopher L. , Schwarz Karen S. 
Published: January 2005

AbstractSeveral theoretical analyses of drug‐taking behavior posit an important mediating role for Pavlovian‐conditioned drug responses that develop as a result of stimulus‐drug pairings imbedded within the self‐administration paradigm. Some of these analyses focus attention on the learning of physiological responses that appear to counteract or compensate for the direct effects of a drug, thereby producing tolerance and encouraging increased drug taking. Others place greater emphasis on the learning of responses that mimic the drug's effect and presumably increase drug taking through a positive incentive mechanism. Our laboratory has been especially interested in the determinants of drug‐induced conditioned changes in body temperature and the roles that such responses might play in drug tolerance, sensitization, and self‐administration. Our research has involved both alcohol and morphine, drugs that produce a similar conditioned thermal response despite the fact that the direct thermal effects of these drug are completely different.In the case of alcohol, our initial studies showed that environmental (cage) cues paired with intraperitoneal (i.p.) injection of the drug acquire the ability to evoke a conditioned hyperthermic response that reduces the hypothermic reaction to ethanol (i.e., tolerance). More recent studies have explored the nature of the events capable of serving as conditioned stimuli (CSs) for such learning. These studies show that interoceptive thermal cues can mediate tolerance to alcohol's thermal effect, but taste cues cannot. The inability of taste cues to mediate tolerance may have special implications for the study of responses that are conditioned during oral self‐administration of alchol, a procedure that offers very salient gustatory cues.In the case of morphine, we have developed an experimental preparation that permits precise temporal control over the CS (a noise‐light compound) and unconditioned stimulus (intravenous morphine) while using techniques that minimize the stress that is induced by drug administration or temperature measurement. These studies show development of a conditioned hyperthermic response that summates with morphine‐induced hyperthermia, resulting in sensitization.The similarity in the conditioned thermal responses induced by alcohol and morphine has encouraged us to consider the possibility that these responses are not directly related to specific drug effects on the thermoregulatory system but instead reflect a nonspecific anticipatory “arousal” response. This notion receives some support from recent studies in our laboratory showing that environmental cues associated with non‐drug reinforcers differing in hedonic value (i.e., shock and sucrose) also acquire the ability to elicit conditioned hyperthermia. It could well be that drug‐induced conditioned changes in body temperature index the acquired motivational processes that maintain drug‐taking and encourage relapse.
Spiroxatrine as a discriminative stimulus: Effects depend on pharmacological history
Authors: Barrett J. E. , Olmstead S. N. 
Published: January 2005

AbstractSpiroxatrine, a compound with effects on both dopamine (DA) and serotonin (5‐HT) neurotransmitter systems, was established as a discriminative stimulus in pigeons. Along with novel anxiolytic nonbenzodiazepine compounds such as buspirone and ipsapirone, spiroxatrine has been suggested to interact at the 5‐HT1A receptor subtype. Following the administration of 0.3 mg/kg spiroxatrine, every 30th consecutive peck on one key produced food, whereas following saline administration, pecks on the alternate key produced food. After dose‐response curves with spiroxatrine were obtained, two pigeons were tested first with buspirone, which, like spiroxatrine, also has effects on both 5‐HT1A and DA systems, and two pigeons were tested first with the more specific 5‐HT1A compounds 2‐mPP (1‐[2‐methoxyphenyl]piperazine) or 8‐OH‐DPAT (8‐hydroxy‐2‐[di‐n‐propylamino]tetralin). All pigeons responded on the drug‐appropriate key when these compounds were the initial drugs substituted for spiroxatrine. Pigeons tested first with 2‐mPP or 8‐OH‐DPAT also responded on the drug‐appropriate key when buspirone was administered in subsequent tests. However, when first tested with buspirone then tested subsequently with 8‐OH‐DPAT, pigeons responded on the saline key at all 8‐OH‐DPAT doses and did so throughout the study whenever any selective 5‐HT1A ligand was substituted. Drug history may enhance or diminish specific stimulus effects of drugs with multiple stimulus dimensions. Drugs with multiple stimulus effects may permit the specific study of behavioral and pharmacological variables that affect the discriminative stimulus effects of drugs and, perhaps, also their behavioral effects under other circumstances.
Individual differences in the discriminative stimulus effects of d‐amphetamine in humans
Authors: Chait Larry D. , Uhlenhuth Eberhard H. , Johnson Chris‐Ellyn 
Published: January 2005

AbstractThe discriminative stimulus (DS) and subjective effects of d‐amphetamine (AMP) were examined in male and female normal healthy adults. Subjects were trained to discriminate between oral AMP (10 mg) and placebo. Of the 100 subjects who underwent discrimination training, 53 reliably learned the discrimination. These “discriminators” (Ds) were compared with the 47 “nondiscriminators” (NDs) on a variety of measures. Ds and NDs did not differ qualitatively in their response to AMP. As a group Ds were more certain than NDs of their ability to discriminate between AMP and placebo and were more accurate in labelling AMP as a stimulant. AMP also had a greater effect for Ds than for NDs on ratings of drug liking and general activity level during the day. Although Ds generally showed a stronger subjective response to AMP, Ds differed significantly from NDs on only 4 of 18 mood scales affected by AMP (2 anxiety scales and analog ratings of “stimulated” and “high”). Ds did not differ from NDs on any of the following measures: body weight, gender, current or lifetime drug use, baseline mood state, subjective response to placebo, or a variety of personality traits. The results demonstrate considerable individual differences in sensitivity to AMP and suggest a relationship between the DS effects of AMP and specific mood states.
Fluoxetine: A serotonergic appetite suppressant drug
Authors: Fuller Ray W. , Wong David T. 
Published: January 2005

AbstractFluoxetine is a selective inhibitor of serotonin uptake that does not have direct effects on catecholaminergic neurons. Like other serotonergic drugs, fluoxetine reduces food intake in rats, and the characteristics of these serotonergic drugs differ from those of amphetaminelike drugs. For instance, fluoxetine and other serotonergic drugs have been reported to suppress stress‐induced eating, to suppress carbohydrate intake selectively, and to suppress eating elicited by insulin injection. Tolerance to the food intake‐reducing effect of fluoxetine has not been seen in experimental conditions in which other anorectic agents have shown tolerance. Clinical trials in overweight, depressed patients and in nondepressed obese subjects have shown the ability of fluoxetine to reduce body weight in humans. Fluoxetine may represent a new appetite suppressant drug that will be useful in the management of obesity.
Comparative hypotensive activity of REV 6207 and enalapril in the conscious furosemide‐treated monkey
Authors: Hubbard John W. , Hintze Thomas H. , Shapiro Jeffrey T. , Kaley Gabor , Smith Ronald D. , Wolf Peter S. 
Published: January 2005

AbstractThe cardiovascular effects of ascending doses (0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg i.v.) of two angiotensin l‐converting enzyme (ACE) inhibitors, REV 6207 and enalapril, were assessed in conscious furosemide‐treated (3 mg/kg s.c.) monkeys. Both ACE inhibitors produced a dose‐related inhibition of the pressor response to angiotensin l (0.66 μ/kg i.v.) with concomitant decreases in mean arterial pressure and no change in heart rate. The calculated ED50 values for REV 6207 (0.316 mg/kg) and enalapril (0.275 mg/kg) were similar and both abolished the pressor response to angiotensin l at a dose of 3 mg/kg. The results of the study show that REV 6207 is a potent nonsulfhydryl‐containing ACE‐inhibitor with blood‐pressure‐lowering activity comparable to enalapril in the conscious monkey with high renin activity.
Current views of zinc as a gastrohepatic protective agent
Authors: Cho C. H. 
Published: January 2005

AbstractThe protective effects of zinc on gastrohepatic lesions induced by various agents are reviewed. Acute gastric glandular mucosal damage produced by parenteral injection of reserpine, cold‐restraint stress or by oral administration of ethanol are prevented by zinc compounds. Hepatic lesions induced by CCl4, ethanol, alkylating agents, or cadmium are also antagonized by zinc ions. The pathological changes evoked by these agents or stress are postulated to be due to free radical production and labilization of biomembranes. These actions are thought to be sequestered or stabilized by zinc. The role of glutathione in the protective action and the involvement of mast cell degranulation in ulceration are further discussed. The data available so far indicate that zinc compounds could be used as protective agents for gastrohepatic diseases.
Psychopharmacology of ritanserin: Comparison with chlordiazepoxide
Authors: Meert T. F. , Janssen P. A. J. 
Published: January 2005

AbstractRitanserin, a central serotonin 5‐HT2 antagonist with complete LSD‐antagonist properties, was compared with the benzodiazepine chlordiazepoxide (CDZ) in different animal models of anxiety. In conflict procedures using electric shock as an inhibitory stimulus, a dose‐related disinhibition was observed with CDZ but not with ritanserin. In various other anxiety tests involving more natural aversive stimuli, ritanserin disinhibited exploratory behavior over a broad dose range while CDZ was marginally active. Clear differences between ritanserin and CDZ were also seen in drug discrimination test procedures. CDZ but not ritanserin had intrinsic discriminative stimulus properties. Furthermore, ritanserin did not generalize with CDZ or with fentanyl, LSD, cocaine, d‐amphetamine, or 8‐OHDPAT. These results suggest that ritanserin is unlikely to possess abuse potential. Unlike the benzodiazepine, ritanserin did not induce motor incoordination or sedation, was devoid of interaction with alcohol, and produced no state dependency. These experimental studies indicate that ritanserin possesses disinhibitory effects on exploratory behavior with a profile of activity diferent from that of benzodiazepines. Ritanserin thus has anxiety‐ and stress‐reducing effects in animal models of anxiety and the drug appears to be an original psychopharmacological compound, clinically characterized as a thymosthenic agent.
Agents enhancing γ‐aminobutyric acid receptor‐coupled chloride ionophore function. Effects in a social interaction model of anxiety in the rat
Authors: Guy Andrew P. , Gardner Colin R. 
Published: January 2005

AbstractA recently described social interaction (SI) model which is sensitive to single doses of benzodiazepines and novel non‐sedative anxiolytic agents has been used. Activities of drugs were compared in both an anxious (animals housed in pairs, tested with a novel partner) and a non‐anxious (animals housed in pairs, tested with the cage mate) condition. Diazepam displays a typical anxiolytic response, increasing SI in the anxious but not in the non‐anxious condition. This was associated with a decrease in aggression (AGG) and in locomotion (LOCO) at higher doses. Seven agents were tested which are thought to enhance central nervous system γ‐aminobutyric acid (GABA)‐mediated neurotransmission by increasing the activity of a receptor‐coupled chloride ionophore system as a major component of their action. Tracazolate, RL348, methaqualone, etomidate, LY81067, and pentobarbitone all significantly increased SI in the anxious but not the non‐anxious condition. In the anxious condition tracazolate and RL348 reduced AGG and all of these compounds except LY81067 reduced LOCO. Methaqualone and etomidate also reduced LOCO in the non‐anxious condition. In addition, an agent which reduces GABA function (picrotoxin) significantly reduced SI in already‐anxious animals, consistent with its known anxiogenic properties. Picrotoxin also reduced LOCO in both conditions. Phenobarbitone induced a non‐specific effect on SI (increased SI in both anxious and non‐anxious conditions), as well as reducing AGG in the anxious condition and LOCO in both conditions. These data suggest that agents enhancing GABA receptor‐coupled chloride ionophore function possess anxiolytic properties which may be attributed to this activity.
Potassium channels as targets for antiarrhythmic drug action
Authors: Colatsky T. J. , Follmer C. H. 
Published: January 2005

AbstractRecent cellular electrophysiologic studies have begun to clarify the basis of antiarrhythmic drug action. The Class I agents have been shown to block cardiac sodium channels in a use‐dependent manner, and the kinetics and potency of sodium channel block correlated with molecular weight and lipid solubility of drug. The Class IA agents, like quinidine, which increase cardiac action potential duration and refractory period in addition to their effects on conduction, also appear to have potent blocking actions on the potassium channels responsible for repolarization in myocardial cells, whereas the Class IB agents, like lidocaine, shorten action potential duration and are relatively specific in their block of sodium channels. In contrast, Class III agents, which prolong the action potential without slowing conduction, appear to exert their primary blocking action on the potassium channel only. Conversion from Class I to Class III electrophysiologic profiles can be achieved by the substitution of electron‐withdrawing groups (e.g., NO2) in place of electron‐donating groups (e.g., NH2) on the aromatic portion of the basic local anesthetic pharmacophore. Class III agents appear to be most effective against ventricular fibrillation and ventricular tachycardia due to re‐entry, but are generally without activity in the 24 hr Harris dog arrhythmia model. Further evaluation of the mechanism of antiarrhythmic drug action will require use of well‐defined arrhythmia models in a combination with a detailed understanding of drug‐channel interactions.
DuP 996 (3,3‐bis(4‐pyrindinylmethyl)‐1‐phenylindolin‐2‐one) enhances the stimulus‐induced release of acetylcholine from rat brain in vitro and in vivo
Authors: Nickolson Victor J. , William Tam S. , Myers Melvin J. , Cook Leonard 
Published: January 2005

AbstractDuP 996, in micromolar concentrations, enhances the K+ ‐stimulated release of acetylcholine (ACh) in rat cerebral cortex, hippocampus, and caudate nucleus slices in vitro, without effect on basal release. DuP 996 has very weak affinity for rat brain muscarinic or nicotinic receptors and does not inhibit acetylcholinesterase activity of rat brain. Upon subcutaneous administration, DuP 996, in doses of 0.1 to 1 mg/kg, increase the output of ACh from the cerebral cortex of awake, freely moving rats. In the mouse, scopolamine‐induced hyperactivity is reduced by DuP 996 in doses of 0.3–0.5 mg/kg (s.c.). In addition, pancuronium HBr‐induced neuromuscular blockade is reversed by DuP 996 (ED50 = 1.7 mg/kg s.c.). The enhancement by DuP 996 of K+ ‐stimulated transmitter release is not limited to the cholinergic system but is also observed in the dopaminergic system in the rat caudate nucleus and in serotonergic systems. K+ ‐stimulated release of gamma‐aminobutyric acid and glutamic acid in rat cerebral cortex, however, is only slightly enchanced by DuP 996, whereas no effects are observed on K+ ‐stimulated release of cortical norepinephrine. DuP 996 may have therapeutic value in the treatment of diseases involving chlinergic and minoaminergic deterioration, like Alzheimer's Disease.
On the mechanism of increased potassium conductance by the potassium channel opener BRL 34915 in Isolated ventricular myocytes
Authors: Liu Bo , McCullough John R. , Vassalle Mario 
Published: January 2005

AbstractThe potassium conductance increased by BRL 34915 (BRL, cromakalim) was studied in single guinea pig ventricular myocytes by using a whole cell voltage‐clamp technique. In control voltage‐clamp recordings, the late current‐voltage relation showed a distinct inward rectification. BRL (1–100 μM) shortened the action potential and diminished or abolished inward rectification but had no effect on the slope conductance and currents flowing during hyperpolarizing clamp steps. BRL did not decrease the slow inward current but accelerated the time constant of activation and amplitude of the outward current. Cd markedly decreased (0.2 mM) or abolished (0.4–0.6 mM) the slow inward current and BRL induced a faster outward shift of late current to a greater value. Glybenclamide (10 μM), a blocker of ATP‐sensitive K+ channels, had little effect of its own on action potential, membrane currents, and I‐V relation. However, in the presence of BRL, glybenclamide abolished BRL effects on action potential and currents and restored inward rectification. It is concluded that the mechanism by which BRL shortens the action potential is a faster growth of an outward current due to the reduction or abolition of the inward rectification of an ATP‐dependent potassium channel. The reduction in force in non‐isolated tissues appears to be an indirect result of the action potential shortening and not of a decreased slow inward current.
Tolerance to drug stimulus control
Authors: Young Alice M. 
Published: January 2005

AbstractA psychoactive drug can acquire discriminative stimulus control of behavior through differential reinforcement processes. Development of tolerance to drug stimulus control reflects a dynamic interaction of conditioning and pharmacodynamic processes. Development of tolerance requires the interplay of drug maintenance regimens appropriate to the agent under study and behavioral conditions that limit an organism's ability to learn a new discrimination. Tolerance to drug discriminative control has four important characteristics: the dose of drug required to evoke stimulus control is increased, the requirement for an increased dose is limited to the period of supplemental drug treatment, the change in potency is pharmacologically specific, and the change may require suspension of discrimination training.
The effects of chronic cocaine administration on brain neurotransmitter receptors
Authors: Goeders Nick E. 
Published: January 2005

AbstractThe nonmedical use of cocaine has continued to increase during the past decade, resulting in considerable interest in the clinical and neurobiological implications of this behavior. A better understanding of the complex neurobiological changes associated with chronic cocaine intoxication may assist in the search for improved methods of treatment in the clinic. In this investigation, chronic daily injections of cocaine for 15 days resulted in opposite effects on dopamine receptor number measured with [3H]sulpiride in the striatum and nucleus accumbens of rats. Binding was increased in the nucleus accumbens but decreased in the striatum. By contrast, benzodiazepine receptors measured with [3H]Ro 15‐1788 were increased in the striatum and cerebellum but decreased in the frontal cortex. Intraventricular injections of 6‐hydroxydopamine resulted in a decrease in the number of benzodiazepine receptors measured in the striatum and reduced the effects of cocaine on these receptors. These data suggest that while chronic cocaine administration may induce changes in dopaminergic activity and dopaminergic receptors, opposite effects may be observed in benzodiazepine receptor number induced either directly by cocaine or indirectly through changes in dopaminergic neuronal activity. Although the significance of these findings is not clear, the results of this investigation suggest a different noncatecholaminergicavenue for future studies to follow.
Noradrenergic processes in the behavioral actions of psychomotor stimulants
Authors: Tessel Richard E. 
Published: January 2005

AbstractAlthough psychomotor stimulants such as cocaine and amphetamine are known to release both norepinephrine and dopamine in brain, most evidence indicates that it is the release of central dopamine rather than that of norepinephrine that mediates the reinforcing, discriminative, and eliciting properties of psychomotor stimulants, i.e., that drug‐induced dopamine release is a necessary and sufficient factor to account for these properties, while drug‐induced norepinephrine release is neither necessary nor sufficient. However, this generally accepted conclusion may not be completely accurate. Evidence is available indicating that psychomotor‐stimulant‐induced increases in norepinephrine release, while possibly not necessary, are sufficient to account at least for the eliciting and discriminative‐stimulus properties of amphetamine‐like drugs. The data supporting this contention are reviewed.
Electroencephalographic and evoked potential methods in human marihuana research: Historical review and future trends
Authors: Struve Frederick A. , Straumanis John J. 
Published: January 2005

AbstractThe sensitivity of electroencephalographic (EEG) signals to variables affecting brain neurophysiological substrate is briefly reviewed. Because this sensitivity extends to numerous pharmacological compounds with central nervous system (CNS) effect, it is suggested that EEG methods may also be useful in studies of human marihuana exposure. EEG investigations of marihuana are grouped by the type of research strategy employed and, within each grouping, the review summarizes salient reported findings as well as methodological issues of concern. The value of using quantitative methods of EEG analyses under blind conditions is stressed. Recent technological developments permitting topographic brain mapping of quantitative EEG variables are described as offering promise for marihuana research and some examples are given. Finally, evoked potential findings in studies of marihuana exposure are reviewed.