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Biomedical subjects

T Ljungberg

Publications and source records attributed to T Ljungberg.

At least 37 records · Page 2Linked to original sources
PubMed1988

Scopolamine reverses haloperidol-attenuated lever-pressing for water but not haloperidol-attenuated water intake in the rat.

The operant lever-pressing response has previously (Ljungberg, Pharmacol Biochem Behav 27: 341-350, 1987) been found to be inhibited by lower doses of haloperidol than the corresponding consummatory act, i.e., water intake. In the present study it was found that the attenuation of the lever-pressing response caused by the neuroleptic, but not the attenuation of the water intake, could be counteracted by scopolamine. The results support the notion that blockade of operant responding by low doses of neuroleptics are probably related to the extra-pyramidal side-effects of neuroleptics seen in the clinic, as both phenomena can be counteracted by anticholinergics. These results therefore conflict with the anhedonia hypothesis put forward as an explanation of the attenuating effects of neuroleptics in operant settings. The findings also have a clear bearing on the role of dopamine in feeding and drinking behavior, as the results implies that different aspects of the control of water intake (i.e., the operant vs. the consummatory phase) are governed by different mechanisms in the CNS.

Animals↗
PubMed1987

A direct comparison of amphetamine-induced behaviours and regional brain dopamine release in the rat using intracerebral dialysis.

An intracerebral microdialysis method was used in awake rats to directly compare the effect of amphetamine on dopamine (DA) release in the striatum and nucleus (n.) accumbens with alterations in behaviour. Amphetamine (0.5-5.0 mg/kg, s.c.) caused a dose-dependent release of DA in both brain regions; however the n. accumbens appeared for the most part more sensitive to amphetamine than the striatum. At each individual dose of the drug, 0.5, 2.0 and 5.0 mg/kg s.c., DA release was closely followed over the time course by the overall behavioural syndrome. Certain components of behaviour showed a regional-specific association with DA release. The intensity of stereotyped head and forepaw movements was closely correlated over the dose range with the amount of DA released in striatum but not n. accumbens. Over the time course, however, the occurrence of this behaviour was delayed compared to increased striatal DA release. In contrast, increased locomotor activity was correlated with the time course change in, and amount of, DA released in n. accumbens by low doses of amphetamine, but not at any dose with DA released in striatum. Repetitive sniffing was better correlated with DA released in n. accumbens than striatum. These in vivo measurements of DA release add further support to the hypothesis that amphetamine-induced stereotypy and locomotion are mediated via DA released in striatum and n. accumbens, respectively. Our data suggest that the occurrence of intense stereotypy rather than locomotor activity at high doses of amphetamine is not due to a selection action in striatum but probably competition between the two behaviours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Impairment of decision making in rats by diazepam: implications for the "anticonflict" effects of benzodiazepines.

Benzodiazepines, used in the clinic as anxiolytics, have in animal models been found specifically to attenuate behavioural suppression caused by response contigent aversive stimuli, non-reward or novelty. The effects have been interpreted in more general terms as "behavioural disinhibition" or "response perseveration" or in more specific terms as reduced "reward delay" or as an attenuation of a "behavioural inhibition system". In a recent publication we have described an experimental test in which decision making in the rat can be studied. The model is derived from ethology, in particular from optimal foraging theory. In order to solve the task, the animal must choose correctly between two options. For each option the probability of its resulting in a reward (water) has to be estimated on the basis of available information and to be related to the cost of performing it. We found that diazepam, in a dose that did not significantly affect the ability to perform the options per se, caused a strong impairment when these options, on the basis of available information, had to be combined into functional sequences in a decision making procedure. The results obtained cannot be explained on the basis of disinhibition or response perseveration. The hypothesis is advanced that benzodiazepines alter decision making in a more nonspecific may, by, for example, affecting the evaluation of the learned significance of stimuli in the environment.

Animals↗
PubMed1987

Disruptive effects of low doses of d-amphetamine on the ability of rats to organize behaviour into functional sequences.

A complex laboratory task was used to test the effects of low doses of d-amphetamine on decision making in the white rat. In particular, the animals' ability to organize their behaviour into functional sequences was studied. The rats were required to choose between two options in order to obtain rewards (water). To solve the problem efficiently, the animal must correctly use information currently available about the reward probabilities and the response costs of the two activities. The results showed that already at a dose of 0.2 mg/kg, by comparison with control, the decision rule was significantly affected and the efficiency of the behaviour decreased. At 1 mg/kg, the rats were generally unable to organize their behaviour into functional sequences resulting in rewards even though they were able to perform the separate behavioural responses required to solve the task, as shown in separate control experiments. Low doses of d-amphetamine have previously been described to be "psychomotor stimulant" and, for example, to increase locomotion and exploration. Our conclusion is that these low doses do not increase behavioural output in an adaptive way. In simple tasks where motor output is directly related to a measure of performance, these doses might be interpreted as causing increased efficiency. However, when tested in our complex decision making task, these doses result in suboptimal behaviour.

Adaptation, Psychological↗
PubMed1987

Blockade by neuroleptics of water intake and operant responding for water in the rat: anhedonia, motor deficit, or both?

Four different neuroleptic drugs, haloperidol, metoclopramide, sulpiride and cis-flupenthixol, were tested for their ability to attenuate an operant lever-pressing response with water as reward and the corresponding consummatory act, i.e., the non-conditioned water intake. All four neuroleptic drugs tested more potently attenuated the operant lever-pressing response than the consummatory water intake, just as the conditioned avoidance response previously has been found to be more potently attenuated than the non-conditioned escape reaction. The results suggest that a certain class of learned behaviors, labelled operant or instrumental behaviors, are more susceptible to the attenuating effects of neuroleptic drugs than the class of behaviors labelled non-conditioned consummatory acts. It was further concluded that the attenuation of the lever-pressing response could be explained by a decreased ability of the animals to initiate or perform the required operant response (i.e., a motor deficit) while the attenuated water intake caused by higher doses of the neuroleptics could be interpreted as a motivational effect (e.g., "anhedonia"). When studying the effects of the neuroleptic drugs it is therefore of great importance to know whether the behavior measured in the particular experimental design used is operant or consummatory. The implications of the findings are discussed.

Animals↗
PubMed1987

Differential effects of the dopamine antagonist remoxipride on apomorphine induced behaviour in the rat.

The effects of the novel substituted benzamide remoxipride on apomorphine induced behaviour in rats was investigated by means of an automatic holeboard apparatus. The ability of remoxipride to antagonise locomotion and gnawing induced by a high dose of apomorphine (5 mg/kg) and inhibition of exploration induced by a low dose of apomorphine (0.05 mg/kg) was tested. It was found that remoxipride in moderate doses potentiate locomotion and inhibit gnawing induced by the high dose of apomorphine while higher doses of remoxipride inhibits both apomorphine induced gnawing and locomotion. The inhibition of exploration following the low dose of apomorphine was not antagonised by remoxipride pretreatment. The results demonstrated that remoxipride has an interesting and unique profile of dopamine antagonistic effects in rat behavioural models.

Animals↗
PubMed1986

Effect of sulpiride on amphetamine-induced behaviour in relation to changes in striatal dopamine release in vivo.

Intracerebral dialysis was used to simultaneously monitor extracellular dopamine (DA) in striatum and behaviour in rats following administration of amphetamine and sulpiride. Amphetamine (2 mg/kg s.c.) caused a marked release of DA into striatal perfusates, an effect which was potentiated in rats pretreated with sulpiride (50 mg/kg s.c.). Amphetamine-induced stereotyped head and forepaw movements were potentiated by sulpiride at a time point corresponding with the enhanced release of DA. In comparison, amphetamine-induced locomotor activity was completely inhibited by sulpiride.

Animals↗
PubMed1986

Intracerebral dialysis coupled to a novel activity box--a method to monitor dopamine release during behaviour.

This paper describes a method for monitoring drug-induced changes in brain dopamine (DA) release and metabolism in the awake rat simultaneous to measurements of behavioural activation. Intracerebral dialysis was combined with a novel activity box based on a circular running track and a simple method for perfusate collection. "Locomotor" and "general" activity were automatically monitored using a system of photobeams lining the track, and stereotyped behaviours were scored by direct observation. Striatal perfusates were analysed for endogenous DA and its main metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), using HPLC with electrochemical detection. This methodology was tested by comparing the behavioural effects of systemically administered amphetamine (2 mg/kg SC) and its central DA releasing action. Amphetamine caused a marked increase in striatal DA release (16-fold) which was followed over the time course by increased locomotion and stereotyped sniffing and head and forepaw movements. The limitations and wider applications of the methodology are discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Locomotion and stereotyped behaviours induced by 1-amino-3,5-dimethyladamantane (D 145) and apomorphine in the rat: a comparison.

The locomotion and stereotyped behaviours induced by the two dopamine agonists, 1-amino-3,5-dimethyladamantane (D 145) and apomorphine in rats have been investigated using a holeboard apparatus. Unlike apomorphine, D 145 did not induce compulsive gnawing, but it did induce locomotion dose-dependently. However, the pattern of locomotion was different from that induced by apomorphine and the locomotion itself was potently antagonized by haloperidol but not by sulpiride; this is the opposite to apomorphine-induced locomotion. This indicates that locomotion induced by dopamine agonists is not a unitary phenomenon but that different 'types' of locomotion, with different pharmacological properties, can be induced. Low doses of D 145, given before apomorphine, reduced apomorphine-induced gnawing and enhanced apomorphine-induced locomotion. The long lasting 'priming' effect known to occur after repetitive injections of apomorphine was not mimicked by D 145. Apomorphine and D 145 are considered to be two specific DA agonists; their behavioural-pharmacological profiles, however, are quite different.

Amantadine↗
PubMed1985

A rapid and simple behavioural screening method for simultaneous assessment of limbic and striatal blocking effects of neuroleptic drugs.

A simple and rapid screening method, where the ability of neuroleptic drugs to antagonise the abnormal pattern of exploration induced by a low dose of d-amphetamine in a 10 min test, was evaluated. The d-amphetamine 2 mg/kg pretreatment induced both an increased locomotion, thought to reflect an increased dopamine transmission in the nucleus accumbens, and weak stereotypies, thought to reflect an increased dopamine transmission in the neostriatum. Haloperidol, chlorpromazine and thioridazine blocked all ongoing behaviours while clozapine and sulpiride, regarded as causing less extrapyramidal side effects in the clinic, only antagonised the d-amphetamine induced locomotion. The findings support the notion that the common site of action for anti-psychotic drugs is blockade of dopamine receptors outside the neostriatum while the blockade of dopamine receptors within the striatum probably are related to the propensity of these drugs to induce the extrapyramidal side effects. It seems possible with this method to screen neuroleptic drugs for their relative potency in blocking limbic and striatal dopamine receptors simultaneously in one short experiment. The method might be used when new anti-psychotic drugs with low incidences of extrapyramidal side effects are sought for.

Animals↗
PubMed1978

A method for simultaneous recording of eight behavioral parameters related to monoamine neurotransmission.

In response to the increasing demand for refined techniques to record drug induced changes in motor activity we have designed and evaluated against observations an automatic test box that quantifies eight defined components of behaviour in rats. Activity, corresponding to the recordings from the commonly used photocell activity boxes. Total, and forward locomotion, expressing the actual distance the rat walks. Corner count, and corner time, reflecting the position of the animal in the box. Hole count, and hole time, expressing the reaction of the rat to an environmental stimulus i.e. holes in the bottom of the test box. Gnawing, which is a direct counting of the number of gnaws made by the animal. The recording parameters relate to our interest in behaviour influenced by monoamine neurotransmission and the result shows that the selected parameters are recorded with high reliability.

Animals↗
PubMed1978

Reliability of two activity boxes commonly used to assess drug induced behavioural changes.

Rats were given different drug treatments known to affect central catecholamine neurotransmission and to induce different types of behavioural changes which were recorded simultaneously by two different types of conventional activity boxes: an Animex activity meter and a photocell cage. All animals were also visually observed simultaneously with the automatic recordings. It was found that the two activity boxes reflected the behavioural changes differently and that the results from the two boxes were not correlated. When comparing the observations with the automatic recordings it was found that some clearly observable changes in behaviour were not reflected as changes in the automatic recordings and conversely that increases or decreases in the recorded motor activity were not always related to any particular changes in behaviour. The results show that motor activity can not be regarded as a simple or homogeneous behaviour that is reliably measured in conventional activity boxes. It is an undescriptive measure consisting of an artificial summation of those components of behaviour that affect the movement-detecting device in the particular box which is used. Practical and theoretical implications of this are discussed.

Animals↗
PubMed1977

Apomorphine-induced locomotion and gnawing: evidence that the experimental design greatly influences gnawing while locomotion remains unchanged.

In a recent study we have shown that it was possible to recognize and record two independent behavioural patterns elicited by apomorphine (s.c.): one behaviour characterized by increased locomotion, sniffing and repetitive head and limb movements and another, characterized by compulsive gnawing. In the present study we have further characterized the gnawing and the locomotion patterns, their dependence on the experimental design and on the test environment. We found that the apomorphine-induced gnawing was easily modified by factors such as the design of the test-box and the habituation of the animal to the test-box. Locomotion, on the other hand was essentially independent of such factors and seemed more compulsive than the so-called "compulsive gnawing".

Animals↗
PubMed1977

Different behavioural patterns induced by apomorphine: evidence that the method of administration determines the behavioural response to the drug.

The behavioural effects of s.c. injected apomorphine was studied on habituated rats in a test-box designed to measure 8 different components of behaviour. Apomorphine, 1 mg/kg, induced two different behaviours: The "G-type" of behaviour characterized by compulsive gnawing and the "LS-type" of behaviour characterized by increased locomotion, sniffing and repetitive head and limb movements. G-type behaviour was induced when apomorphine, dissolved by heating, was injected s.c. into the flank of the animal. LS-type behaviour was induced both when apomorphine, dissolved by heating, was injected s.c. into the neck and when it was dissolved by heating together with a high concentration of ascorbic acid (1 mg/ml) and injected s.c. into the flank. G-type behaviour could not be elicited by changing the dose which induced LS-type behaviour or vice versa. We therefore conclude that these different behavioural effects of apomorphine were not dose--response effects but were elicited by at least two different synaptic mechanisms in the brain. Experimentally induced changes from one of these apomorphine-induced behaviours to another can therefore not merely be interpreted as a change in the intensity of the behavioural response as is done in e.g. commonly used stereotypy rating scales.

Animals↗