Biomedical subjects

J L Slangen

Publications and source records attributed to J L Slangen.

At least 19 recordsLinked to original sources

PubMed1998

[Cognitive and psychotic effects after cessation of chronic cannabis use].

Establishment of residual cognitive and psychotic effects (effects present at the time that all active cannabinoids are eliminated from the body) putatively produced by prolonged heavy cannabis use is difficult, because of many confounding variables like slow elimination of active cannabinoids, lack of supervision during abstinence, poor use of well-matched control groups and the presence of withdrawal symptoms. Residual cognitive effects were observed in some but not in all tests after prolonged heavy cannabis use. The effects were mostly mild. The relationship of cannabis use, psychotic effects and schizophrenia was unclear; the cannabis conceivably gave relief, but it also appeared that cannabis caused schizophrenia in young people and (or) enhanced the symptoms, especially in young people poorly able to cope with stress or in whom the antipsychotic therapy was unsuccessful.

Adolescent↗

PubMed1996

Effects of infusion of cholinergic drugs into the prefrontal cortex area on delayed matching to position performance in the rat.

Rats trained on a Delayed Matching To Position (DMTP) task displayed mediating behavior during delays to solve the task. Infusion of the cholinergic antagonist scopolamine into the medial Prefrontal Cortex area (mPFC), dose dependently impaired performance independent of delay. These results indicate that scopolamine does not specifically affect working memory. Infusion of the cholinesterase inhibitor physostigmine, muscarinic subtype receptor antagonists, the dopamine (D1) antagonist SCH23390, and of the GABA-A receptor antagonist bicuculline, did not affect performance in the DMTP task. In a post-hoc analysis scopolamine was found to impair discriminability in a delay-dependent manner only in animals that used mediating behavior in the majority of the trials. Furthermore, a time sampling method indicated that scopolamine infusions into the mPFC disrupted mediating behavior during the task. Results suggest that cholinergic systems in the mPFC play a role in directing attention to task relevant behavior.

Animals↗

PubMed1995

The object delayed non-matching to sample task in rats does not depend on working memory.

Four rats were trained on an object delayed non-matching to sample task to measure working memory (WM). On separate trials a sample object was presented to the rat, which was presented again along with another object after a 3 s delay rats were rewarded with food if they chose the novel object. In this procedure the choice objects are positioned in a fixed order (the novel object was positioned at first, followed by the sample object). When the order of placement of the choice objects was reversed performance dropped from 87% to 28% correct, showing that the rats always chose the object that was first positioned into the choice area. When the order of positioning of the choice objects was randomized during training, rats were not able to learn the task. It is suggested that performance is based on a discrimination between choice objects instead of WM.

Animals↗

PubMed1995

Predictive validity of the potentiated startle response as a behavioral model for anxiolytic drugs.

The fear-potentiated startle (PSR) paradigm is a putative behavioral model for the determination of anxiolytic properties of drugs. The present study further investigated the predictive validity of the model. Predictive validity is high, when only drugs clinically used as anxiolytics attenuate PSR dose dependently. Results showed that startle potentiation decreased dose dependently after the administration of the anxiolytics CDP (2.5-10 mg/kg, IP) and alprazolam (1-3 mg/kg, IP). After administration of the clinically non-anxiolytic drugs amitriptyline (2.5-10 mg/kg, IP), carbamazepine (5-20 mg/kg, IP), fentanyl (0.0025-0.04 mg/kg, SC), naloxone (2.5-10 mg/kg, IP), nicotine (0.4-1.6 mg/kg, IP), alcohol (500-2000 mg/kg, IP), and d-amphetamine (0.6-2.4 mg/kg, IP), a dose-dependent decrease in startle potentiation was not found. The PSR correctly discriminated most of the drugs tested in clinically anxiolytic and clinically non-anxiolytic drugs. However, haloperidol behaved as a false positive, and results of nicotine and alcohol were at variance with results reported by others.

Alprazolam↗

PubMed1995

Effects of oxazepam on event-related brain potentials, EEG frequency bands, and vigilance performance.

Eighteen males performed two vigilance tasks with static and dynamic stimuli under the influence of oxazepam (20 and 40 mg) in a placebo-controlled, double blind, crossover design. Oxazepam dose-dependently impaired overall level of performance and aggravated the decrement with time in measures of accuracy and sensitivity relative to placebo. The drug reduced the amplitudes of the P1, N1, P2N2, and P3 (dose-dependently) waves of event-related potentials (ERPs). Oxazepam aggravated the linear decline with time of the P3 amplitude only. Oxazepam impaired accuracy was related to deterioration of central processing involved in stimulus discrimination (P2N2). Impairment of response-related performance measures (RT and RI) was associated with processing manifest in the P1, N1, and P3 waves. Oxazepam effects on the amplitudes of N1 and P3 correlated with drug effects on power in alpha 1 (8-10 Hz). Drug effects on overall performance and alpha were also related; the drug effect on response speed correlated only with the drug effect on beta 1 (12.5-21 Hz). Effects of time-on-task on performance and EEG were unrelated, but oxazepam induced performance declines with time may have been caused by declines in resource allocation, as manifest in the amplitude of P3. Time effects on EEG power bands and ERP amplitudes were not significantly related to the time course of oxazepam activity. A curious dissociation emerged: both oxazepam and time-on-task impaired performance, but the drug induced a decrease of theta and alpha 1 power, whereas time-on-task increased power. Various processes play a role in performance decrements with time, and various aspects of processing may be involved in signal-detection measures which makes terms such as sensitivity quite meaningless. So-called computational processing was indistinguishable from energetic processes, which questions the validity of the distinction between these two domains. Explanations of EEG activity in terms of a unidimensional theory of arousal are untenable.

Adult↗

PubMed1995

Relation between stimulus discriminability and response bias in a delayed conditional discrimination task in the rat.

The present study investigated whether changes in response bias (log b) affect discriminability (log d) in a delayed conditional discrimination (DCD) task. Eight rats were trained on an DCD task and response bias was manipulated by changing the reinforcement ratio (RR) for correct responding on the two response alternatives. Three findings emerged. First, changes in RR produced changes in log b and the magnitude of these changes was related to the value of the RR. Second, log d was affected by changing RRs. Third, the effect of changes in RR on log b was larger after longer delays. These results suggest that log d and log b are not independent and it is concluded that changes in response bias (log b) may affect the discriminability measure log d. This implies that changes in log d may be mediated by changes in response bias and it is therefore recommended that log d and log b values are both reported when investigating effects of, for example, pharmacological manipulations on DCD performance.

Animals↗

PubMed1995

Cholinergic drug effects on a delayed conditional discrimination task in the rat.

The centrally acting cholinergic antagonist scopolamine (0.025-0.10 mg/kg ip) and the peripherally acting cholinergic antagonist methyl-scopolamine (0.01-0.10 mg/kg) dose dependently impaired discriminability independent of delay in a delayed conditional discrimination task that precludes use of mediating behavior. This indicates that scopolamine does not specifically affect working memory. Drugs that enhance cholinergic transmission neither improved discriminability nor attenuated scopolamine-induced impairments. In a post hoc analysis scopolamine was found to impair discriminability in a delay-dependent manner in rats that performed at a high level in pretest sessions. Methyl-scopolamine impaired performance independently of delay in these rats. The authors suggest that a ceiling effect at short delays produced this Drug x Delay interaction of scopolamine in the best performing rats.

Animals↗

PubMed1994

Adrenoceptors and dopamine receptors are not involved in the discriminative stimulus effect of the 5-HT1A receptor agonist flesinoxan.

Using a two-lever operant drug discrimination procedure, rats were trained to discriminate the 5-HT1A receptor agonist, flesinoxan (0.5 mg/kg i.p.), from saline. Hereafter, several non-serotonergic drugs were tested in generalization and antagonism tests. The flesinoxan stimulus did not generalize to the stimuli of either the alpha 1-adrenoceptor antagonist, prazosin, the alpha 2-adrenoceptor agonist, clonidine, the dopamine receptor agonist, apomorphine, the dopamine receptor antagonists, haloperidol and pimozide, the benzodiazepine receptor agonist, chlordiazepoxide, nor to the peripherally acting vasodilator, hydralazine. In antagonism studies, prazosin, haloperidol, pimozide and the alpha 2-adrenoceptor antagonist, idazoxan, failed to block the flesinoxan stimulus. In substitution tests, however, flesinoxan partially generalized to idazoxan and completely to the alpha 2-adrenoceptor antagonist, yohimbine. The affinities of yohimbine and idazoxan for the 5-HT1A receptor may explain the latter result. The present findings suggest that the central mechanism through which flesinoxan exerts its discriminative stimulus effects does not involve alpha 1- and alpha 2-adrenoceptors, dopamine and benzodiazepine receptors. Finally, the results with the blood pressure lowering agents, hydralazine, clonidine and prazosin do not support the suggestion that the centrally mediated blood pressure lowering effects of flesinoxan contribute to its internal stimulus effect.

Animals↗

PubMed1994

Effects of oxazepam on eye movements and performance in vigilance tasks with static and dynamic stimuli.

The aim of the present study was to determine whether in a task with stimuli inducing frequent saccadic eye movements, ingestion of oxazepam impairs performance more than in a task in which the stimuli remained fixed at the same location, due to effects of oxazepam on the ocular system. Eighteen males performed a vigilance task with static and dynamic stimuli under the influence of oxazepam (20 and 40 mg) in a placebo-controlled, double blind, crossover design. Oxazepam (40 mg) had a larger effect on vigilance performance in the first part of the dynamic task, relative to its static counterpart. Oxazepam also had an effect on oculomotor behavior, but this effect was unrelated to impaired performance. There were dose-dependent effects of oxazepam on absolute, overall level of performance but not on the decrement with time. The non-dose-dependent aggravation of the decrement in correct detections, caused by the drug, could only partly be accounted for by pharmacokinetics and increased eyelid closures, and was also caused by pharmacodynamic effects of the drug, such as those on attention. Different effects were noted for the two signal detection measures of response behavior, B" and RI.

Adult↗

PubMed1994

Effects of oxazepam on performance and event-related brain potentials in vigilance tasks with static and dynamic stimuli.

Eighteen males performed two vigilance tasks with static and dynamic stimuli under the influence of oxazepam (20 and 40 mg) in a placebo-controlled, double blind, crossover design. Oxazepam (40 mg) caused impaired performance in the early part of a task with stimuli inducing frequent saccadic eye movements (dynamic task), relative to a task in which the stimuli remained at the same location (static task). This could not be explained by effects of the drug on oculomotor behavior. A larger diameter of the pupil in the dynamic task indicated that performance on this task may have required more effort. Stimulus processing requirements were higher in the dynamic task, as suggested by event-related brain potentials (ERPs), in particular the P3 wave; i.e., more resources had to be allocated in this task. This (additional) investment of resources appeared impossible after administration of oxazepam (40 mg). The conclusion was that tasks eliciting frequent eye movements require more effort and processing resources.

Adult↗

PubMed1994

Validity of a delayed conditional discrimination task as a model for working memory in the rat.

A delayed conditional discrimination (DCD) task in the rat was modified by requiring a response on an admission lever at the end of each delay. This requirement proved effective in precluding the use of positional cues as mediating behavior. Furthermore, validity of the procedure was assessed by examining how performance changed as a result of: length of the delay, retroactive and proactive interference, and encoding time. Results showed that log d, a measure of stimulus discriminability, decreased on longer delays (Experiment 1); decreased when an interfering stimulus was presented during delays (Experiment 2); decreased when the intertrial interval was made shorter (Experiment 3); and decreased when the sample stimuli were presented for a shorter period of time (Experiment 4). Log b, an index of bias, remained low throughout the study, indicating that no significant response bias was present. Taken together, the results support the notion that this modified DCD task is a valid model for working memory that effectively precludes the use of positional cues as mediating behavior in the rat.

Acoustic Stimulation↗

PubMed1994

Discriminative stimulus effect of flesinoxan: effect of 5-HT1A antagonists and PCPA.

Rats were trained to discriminate 0.3 mg/kg (IP) flesinoxan from saline in a standard two-lever operant procedure and thereafter subjected to generalization and antagonism tests with the 5-HT1A receptor agonist ipsapirone and the beta-adrenergic/5-HT1 receptor antagonist pindolol. Ipsapirone (3.0 mg/kg) completely substituted for flesinoxan. Both the flesinoxan (0.3 mg/kg) and the ipsapirone cue (3.0 mg/kg) were dose-dependently blocked by (+/-)-pindolol. In a second group of rats, trained to discriminate 0.5 mg/kg (IP) of flesinoxan from saline, the putative 5-HT1A antagonist NAN-190 (in the dose range of 1.0 to 6.0 mg/kg) partially blocked the cue of flesinoxan. Generalization studies revealed that the flesinoxan cue could not be mimicked by NAN-190 (3.0 mg/kg). Finally, rats were pretreated with the 5-HT depletor parachlorophenylalanine (PCPA) and thereafter tested with the flesinoxan training dose (0.5 mg/kg). PCPA pretreatment did not significantly attenuate the recognition of the flesinoxan cue. The present results are in agreement with previous findings concerning the stimulus effect of flesinoxan and point to a mechanism that involves the activation of 5-HT1A receptors in the brain. Depletion of 5-HT did not significantly affect the stimulus effect of flesinoxan, suggesting that presynaptic 5-HT1A receptors do not play a crucial role in the mechanism underlying the stimulus effect of flesinoxan.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1993

The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity.

To investigate a dopaminergic component in the discriminative stimulus properties of buspirone, rats were trained to discriminate 2.5 mg/kg buspirone from saline, using a two lever, food-rewarded, fixed ratio 10 operant procedure. To test the dopamine-2 (D2) antagonist action of buspirone, a second group of rats was trained to discriminate 0.16 mg/kg apomorphine from saline. In addition to a complete generalization to 8-OH-DPAT, the D2 antagonists haloperidol, R 79598 and sulpiride showed a partial generalization to buspirone. The benzodiazepine ligands chlordiazepoxide and bretazenil did not generalize to the buspirone cue. Buspirone (2.0 mg/kg) completely blocked the apomorphine cue in the apomorphine trained rats. Haloperidol, R 79895 and sulpiride also blocked the apomorphine cue, although at doses much smaller than the doses needed to evoke buspirone responding in the buspirone trained group. 8-OH-DPAT did not antagonize apomorphine. It was concluded that the D2 action of buspirone partially contributes to its discriminative stimulus properties. Mediation of the buspirone cue by 5-HT1a receptor activation seemed predominant. Further, buspirone can act as a full D2 antagonist in drug discrimination. A model was proposed suggesting a compound discriminative stimulus complex of buspirone with a dominant 5-HT1a component that overshadows a less pronounced D2 component.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Effects of bromazepam on single-trial event-related potentials in a visual vigilance task.

Thirty females performed a visual vigilance task under the influence of bromazepam (6 and 12 mg) in a placebo-controlled, double blind, experiment. Measures employed were percentage of hits, percentage of false alarms, response latency (RT), A' (sensitivity), B" (cautiousness), and RI (responsivity), as well as signal- and non-signal event-related potentials (ERPs). Bromazepam did not aggravate the normally occurring decrement in performance in vigilance tasks, but had an effect on overall level of performance: accuracy was reduced under the influence of the drug, but speed improved. A Drug x Period interaction for cautiousness (B") indicated increasingly less cautiousness with bromazepam, which probably contributed to faster motor responses (and more errors) than in the placebo group. The ERP data suggest that the effects of bromazepam are already manifest in the early stages of information processing (attention-detection) as mirrored by a drug effect on N1 amplitude. Deterioration at this early stage may affect later processing stages (P2-N2 amplitudes). As a result, subjects under the influence of the drug probably accumulate less signal evidence for their final evaluation.

Adult↗

PubMed1992

Testosterone as appetitive and discriminative stimulus in rats: sex- and dose-dependent effects.

Stimulus properties of subcutaneously injected testosterone were studied in male and female rats. In a conditioned place preference procedure, dose-dependent effects (doses: 0, 0.5, and 1 mg/kg) were observed in males. In females, no place preference could be established (doses: 0, 1, and 3 mg/kg). In addition, 1 mg/kg testosterone acquired discriminative stimulus control in male rats in a taste aversion procedure. Animals injected with this hormone prior to saccharin-LiCl pairings and with its vehicle prior to saccharin-NaCl pairings suppressed fluid intake following the administration of testosterone and not following the administration of the vehicle. Subsequent generalization tests revealed dose-dependent stimulus control of this hormone (range of substitution doses: 0.125-2 mg/kg). It is concluded from the results that at least pharmacological (supraphysiological) doses of testosterone may act as appetitive stimuli in male rats, but not in female rats. Furthermore, in male rats (pharmacological doses of) testosterone also possess discriminative stimulus properties.

Animals↗

PubMed1992

Temporal characteristics of appetitive stimulus effects of luteinizing hormone-releasing hormone in male rats.

Conditioned place preference, induced by intraperitoneal injections of 5 micrograms/kg luteinizing hormone-releasing hormone (LHRH), was studied by varying the interval between the injection of LHRH and the conditioning sessions. Place preference was investigated for five presession intervals (0, 15, 45, 75, and 120 min) in separate groups of gonadectomized male rats provided with a subcutaneous testosterone implant. It was shown that the presession interval is an important parameter in the development of LHRH-induced conditioned place preference. Place preference was not observed after conditioning with intervals of 0, 75, and 120 min. With 15 and 45 min, however, a reliable preference was induced by LHRH. This study provides insight into the onset and offset of the appetitive stimulus properties of LHRH in male rats.

Animals↗

PubMed1992

Assessment of the stimulus properties of anxiolytic drugs by means of the conditioned taste aversion procedure.

The conditioned taste aversion (CTA) procedure has recently been described as a more rapid alternative to two-lever operant procedures in drug discrimination research. We trained different groups of rats to discriminate the benzodiazepine chlordiazepoxide (CDP, 20 mg/kg) or the 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.4 mg/kg) from saline by means of the CTA procedure. The results were in agreement with findings from two-lever operant drug discrimination procedures. However, discrimination training took 40 sessions in the case of CDP and 72 sessions for 8-OH-DPAT, which is comparable to results obtained with two-lever operant procedures. Dose-response curves were determined and generalization tests were performed for different benzodiazepine and nonbenzodiazepine anxiolytics. Baseline behavior deteriorated in the course of generalization and substitution testing, thus preventing further generalization testing. Our experience is that the use of the CTA procedure in drug discrimination research does not have sufficient advantages over traditionally used procedures to replace the latter.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Visual stimulus change and the orienting reaction: event-related potential evidence for a two-stage process.

In a previous study it was found that infrequent deviant visual stimuli, in a series of standards, elicited event-related potentials (ERPs) with enhanced P2-N2s and P3 amplitudes, suggesting that these parameters reflect processes related to the orienting reaction (OR). In the present study a similar oddball series was presented against the background of a second class of stimuli. With respect to the latter stimuli, subjects had to perform either a very involved (hard) or an easy task. EEG was recorded to oddball (probe) stimuli from Oz, Pz, Cz, and Fz. Analysis of average ERPs revealed that, in the easy condition, deviant probes elicited both enhanced P2-N2s and enhanced P3s, relative to the standards. In contrast, in the hard condition P2-N2, but not P3, was enhanced by stimulus change. In addition, overall P3 amplitude to probes was smaller in the hard condition (sequence-independent load effect). Analysis of single-trial ERPs (SERPs) with orthogonal polynomial trend analysis largely replicated these effects. In addition, SERP analysis also revealed a sequence-independent load effect on P2, as well as a decreasing P3 to deviant stimuli in the Easy condition, which was observed at Cz and Fz, but not at Pz or Oz. The results are interpreted as suggesting that P2-N2 and P3 reflect different stages of the OR, one of automatic and one of capacity-limited processing.

Adult↗