Management of coronal discolouration following a regenerative endodontic procedure in a maxillary incisor.

Pulpal necrosis and infection in an immature anterior tooth subsequent to traumatic injury is a challenging situation. Regenerative endodontics, resulting in continued development of the tooth, provides a biological response to this clinical challenge. Regenerative endodontic procedures require disinfection of the infected root canal and sealing of the pulp canal space. Mineral trioxide aggregate (MTA) provides a good seal, is biocompatible and allows the formation of a hard tissue to occur within the root canal. MTA, however, can lead to significant staining of the crown of the tooth that is difficult to mask. This case report describes the management of discolouration in an 11 year old girl subsequent to a regenerative endodontic procedure in an immature traumatized maxillary central incisor.

A model for carbamate and organophosphate-induced emesis in humans.

In human volunteers, studies to assess the adverse effects of the carbamate anticholinesterase physostigmine showed that the intramuscular dose observed to induce emesis in 50% of subjects tested (ED50) was 28.1 (23.5-120.7) micrograms/kg. This dose reduced whole blood cholinesterase (ChE) activity to 60% of control values. Studies in marmosets to assess the behavioural toxicology of physostigmine showed that the corresponding ED50 and ChE activity values were 34.3 (21.5-55.8) micrograms/kg and 66% respectively. Sarin was also shown to induce emesis in marmosets, but only at doses that reduced erythrocyte ChE activity to 12% of control values. These data seem also to correspond with reports of organophosphate poisoning in humans. It is concluded that the marmoset may be a very good model of both carbamate and organophosphate-induced emesis in humans.

Comparison of the discriminative stimulus properties of clonidine and amphetamine in rats.

Rats were trained to discriminate d-amphetamine (1.0 mg/kg) or clonidine (0.06 mg/kg) from saline in a standard, two-lever procedure with food reinforcement (n = 6). The similarity between the discriminable properties of amphetamine and clonidine was both partial and asymmetrical. Cross tests with amylobarbitone and chlordiazepoxide in rats trained with clonidine suggested that a major component of the clonidine stimulus may be general sedation. Pretreatment with the alpha 2-adrenoreceptor antagonist, piperoxane partially antagonized the discriminative stimulus produced by clonidine. The alpha 1 antagonist, phenoxybenzamine failed to alter the clonidine stimulus. Although amphetamine and clonidine may share some elements in common, this may not represent a noradrenergic component in the amphetamine discriminative stimulus since noradrenergic mediation of the clonidine stimulus was not established.

Interaction of cocaine with chlordiazepoxide assessed by motor activity in mice.

1 Effects of a range of doses of cocaine and chlordiazepoxide given separately and as mixtures were determined on the spontaneous locomotor activity of mice. 2 Cocaine increased locomotor activity (walking) during 3 or 5 min trials in a dose-related manner. 3 Chlordiazepoxide had little effect on the total amount of locomotor activity except for depression at very high doses. A lower dose of chlordiazepoxide increased activity at the beginning of the trials only. 4 Mixtures containing certain doses of cocaine and chlordiazepoxide increased locomotor activity ot a much greater extent than cocaine alone. This high level of activity was manifested throughout 5 min trials. 5 This action of cocaine is similar to that of amphetamine.

Comparison of the discriminative stimulus properties of cocaine and amphetamine in rats.

1. Water-deprived rats were trained to press either the left or the right bar in a test chamber according to whether they were injected with a central nervous system stimulant or 0.9% w/v NaCl solution (saline). Correct responses were reinforced with water. 2. Different groups of rats learned to discriminate amphetamine or cocaine from saline. Dose-response curves and ED50 values were then determined in brief test sessions when no responses were reinforced. 3. In a crossover study, cocaine was tested in the rats trained to discriminate amphetamine from saline, and vice versa. The two drugs were largely interchangeable, but the ED50 values were increased, indicating a possible, subtle difference in their discriminative stimulus properties. 4. The results indicate the importance of complete crossover designs in combination with dose response determinations when attempting to classify drugs according to their discriminable properties.

Comparative potencies of amphetamine, fenfluramine and related compounds in taste aversion experiments in rats.

1 Rats failed to drink a flavoured solution when its consumption had been followed by injection of amphetamine (conditioned taste aversion).2 There was very little difference between the potencies of (+)- and (-)-amphetamine.3p-Chloromethamphetamine was a more potent aversive agent than methamphetamine.4 Strong taste aversions were also conditioned with other congeners of amphetamine. The rank order of potency was: fenfluramine > chlorphentermine >p-hydroxyamphetamine.5 Cocaine induced only moderate taste aversions, even at high doses.6 Aversive potency did not appear to be correlated with known neurochemical actions of the drugs or with behavioural stimulation, but appeared to be a central action which may have been linked to anorexigenic potency or time course of action.

A comparison of some behavioural effects of amphetamine and electrical brain stimulation of the mesolimbic dopamine system in rats.

Separate groups of rats were trained to press a lever on either a fixed-ratio 40 or fixed-interval 1-min schedule of food reinforcement. Amphetamine increased low rates and decreased high rates of responding. In contrast, electrical stimulation of rewarding sites in the ventral tegmentum was effective only in decreasing high response rates. Stimulation of non-rewarding sites had little effect upon either low-or high-rate responding. Another group of rats was trained to discriminate between amphetamine (1.0 mg/kg) and saline in a standard two-lever procedure with food reinforcement. The internal stimulus produced by the stimulation of rewarding sites did not substitute readily for the discriminative stimulus produced by amphetamine. The results suggest that the operant response-rate decreasing property of amphetamine may be partially mediated through the mesolimbic dopamine system. However, this system may not play a prominent role in mediating either the operant response-rate increasing or discriminable properties of this drug. The idea that the abuse liability of amphetamine may be related to the ability of the drug to interact with one of the central reward systems is discussed.

Role of training conditions in discrimination of central nervous system stimulants by rats.

Amphetamine and some relate compounds were compared in rats trained to discriminate (+)-amphetamine (0.4, 1.0 or 1.6 mg/kg) or cocaine (10.0 mg/kg) from the non drug condition in a standard, two-bar procedure with food reinforcement (n=5-6). Amphetamine and cocaine were generalized completely with each other, in most cases at dose levels which did not greatly reduce the overall numbers of responses. The ED50 values for amphetamine and cocaine varied with the drug and dose used for training, and it was concluded that the stimuli produced by the two drugs were similar but may not be identical. There was an excellent correlation between ED50 values derived from indices of bar selection and percentage-responding on the drug-appropriate bar. Apomorphine was generalized with amphetamine only in the rats trained with the higher doses of amphetamine, and only when administered in doses which greatly reduced the overall number of responses. Para-hydroxyamphetamine increased responding on the drug-appropriate bar only when administered in high doses to the rats trained with the lowest dose of amphetamine (0.4 mg/kg). The results strengthen the evidence that the particular drug and dose level used for training can significantly affect the outcome of generalization tests, and challenge the notion that the discriminability of drugs is an immutable property that is amenable to absolute measurement.

A conveyor belt task for assessing visuo-motor coordination in the marmoset (Callithrix jacchus): effects of diazepam, chlorpromazine, pentobarbital and d-amphetamine.

A conveyor belt task for assessing visuo-motor coordination in the marmoset is described. Animals are motivated by apple, a preferred food, under a state of minimal food deprivation. The apparatus used was designed to test animals within their home cages and not restrained in any way, thus avoiding possible confounding factors associated with restraint stress. Stable baseline levels of performance were reached by all animals in a median of 24 sessions. Performance was shown to be differentially sensitive to the effects of four psychoactive drugs. Moderate doses of diazepam, chlorpromazine and pentobarbital disrupted visuo-motor coordination in a dose-related manner. The possibility that disruption of performance observed at higher doses may have resulted from non-specific actions of these drugs such as decreases in feeding motivation were not supported by results from ancillary experiments. Changes in performance characteristic of high dose effects were similar in nature to changes observed when the degree of task difficulty was increased. Doses of d-amphetamine up to and including those reported to produce signs of stereotypy failed to influence performance. The potential of the conveyor belt task for measuring visuo-motor coordination in both primate and rodent species is discussed.

Does conditioned nausea mediate drug-induced conditioned taste aversion?

Two antiemetic drugs were tested on the expression of taste aversions previously conditioned in rats with lithium, amphetamine or morphine. Neither prochlorperazine nor scopolamine administered prior to testing attenuated established aversions, although both drugs are known to have antiemetic effects in other species. Negative findings were obtained with a range of dose of prochlorperazine and scopolamine, with strong and weak aversions, with one- and two-stimulus tests, in a repeated one-stimulus extinction procedure, with between- and within-group designs and with hooded, albino, male and female rats. The results do not support the widely accepted hypothesis that conditioned nausea mediates conditioned taste aversion.

Animal models in cognitive behavioural pharmacology: an overview.

Most studies in cognitive behavioural pharmacology have used rodents as subjects and simple learning tasks. This approach is regarded as acceptable because the cognitive abilities of rats may not differ from those of non-human primates and the modelling in animals of those advanced cognitive abilities possessed by humans may be of limited utility. A strength of many existing models lies in their construct validity. However, the face, concurrent and predictive validities of many animal models are low. In part, this is due to the need to take account of species specific characteristics in experimental design. Thus, inter-species differences in learning may be explained not by differences in cognitive ability but by differences in species specific morphological, physiological and behavioural characteristics. Features of the 'ideal' animal model of human cognitive function are listed and potential strategies for future research in cognitive behavioural pharmacology assessed.

Suppression of fixed-interval responding by flavour-amphetamine pairings in rats.

Amphetamine is a potent and very effective drug for conditioning taste aversions, but much less is known about the possible effects of flavour-amphetamine pairings on aspects of behaviour other than eating and drinking. Rats were trained to press bars for water reinforcers delivered on a fixed-interval one-min schedule. Flavoured reinforcers were then substituted for the water and post-session injections of amphetamine (1 mg/kg) were given. Even a single flavour-amphetamine pairing produced some disruption of responding for that flavour, whereas 3 pairings almost completely suppressed responding (both bar-pressing and drinking). In the same rats, flavours paired with saline injections did not suppress responding. Amphetamine (1mg/kg) injected before sessions of responding for plain water disrupted the temporal pattern of fixed interval responding without affecting the total numbers of bar-presses or the amounts of liquid consumed. Omitting primary reinforcement (water) throughout a single session also failed to suppress responding. The conditioned effects of the flavour were therefore different from the effects of either the unconditioned stimulus (amphetamine) or of an extinction procedure.

Amphetamine-induced taste aversion demonstrated with operant behaviour.

Amphetamine can be used to condition strong taste aversions, but little is known about the possible effects of flavour-amphetamine pairings on operant behaviour. Rats were trained to press bars for water reinforcers delivered after every 40 responses (FR 40). Flavoured reinforcers were then substituted for the water and post-session injections of amphetamine (1 mg/kg) were given. Even a single flavour-amphetamine pairing produced some decrement in responding for that flavour, whereas three flavour-amphetamine pairings almost completely suppressed responding. In the same rats, a flavour which was paired with saline injections did not suppress responding. Flavour-amphetamine pairings can therefore have a powerful influence on operant behaviour and the different outcomes of flavour-conditioning and self-administration procedures cannot be attributed simply to the type of response required from the rat.

Amphetamine-induced hypodipsia and its implications for conditioned taste aversion in rats.

According to the conditioned anorexia hypothesis, conditioned taste aversions occur when flavour stimuli are classically conditioned to the anorexigenic or hypodipsic effects of drugs. The effects on water intake of a range of doses of amphetamine and of several related compounds have therefore been examined in an attempt to correlate their known potentices in tate aversion experiments with their hypodipsic potencies (+)-Amphetamine was more potent than (-)-amphetamine in suppressing water intake but under similar experimental conditions, the isomers were equipotent in the conditioning of taste aversions. Methamphetamine and p-chloromethamphetamine were equipotent in suppressing water intake, but the latter was a more potent agent for conditioning taste aversions. Furthermore, fenfluramine produced taste aversions at doses well below those which suppressed water intake. It was concluded that the ability of the drugs to induce taste aversion was not related to their unconditioned, hypodipsic effects. However, it was confirmed that when drugs with different durations of action are compared for anorexic or hypodipsic potency, the outcome can be greatly influenced by the time over which measurements are made.

Factors influencing flavour aversions conditioned with amphetamine in rats.

Rats would not drink distinctively flavoured solutions after their previous ingestion had been followed by injection of amphetamine (1 mg/kg). In the same rats, intake of flavoured solutions followed by saline injections was not suppressed. Providing the rats with cues as to the location of flavoured solutions paired with amphetamine did not alter either the speed of development or the final severity of the aversion. Neither increasing the interval between presentation of the flavour and injection of amphetamine, nor decreasing baseline drinking levels, altered the final degree of aversion. The aversion became progressively weaker as the dose of amphetamine was reduced, but it was detectable at doses as low as 0.1 mg/kg. Further decreases in dose did not enhance intake of flavours paired with amphetamine, even when combined with reductions in baseline drinking brought about by reduced fluid deprivation and flavour palatability. The results are discussed in relation to the conditions in which amphetamine has been shown to exhibit either rewarding or aversive properties.

Behavioural toxicity of anticholinesterases in humans and animals--a review.

1. Available information describing the behavioural changes induced by anticholinesterases in humans and animals is reviewed. 2. Very little confidence can be placed in existing descriptions of the behavioural effects of anticholinesterases in humans. 3. Although data from animal experimental studies is reliable, the information obtained is relatively superficial. 4. It is concluded therefore, although much information is available, surprisingly little is known of the behavioural changes induced by anticholinesterases.