Biomedical subjects

T Sagvolden

Publications and source records attributed to T Sagvolden.

At least 19 recordsLinked to original sources

PubMed2002

Guidelines and algorithms for the use of methylphenidate in children with Attention-Deficit/ Hyperactivity Disorder.

OBJECTIVE: To review published algorithms for guiding the use of methylphenidate (MPH) in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. METHODS: A consensus roundtable of 12 experts was convened to review the evidence for the safety and efficacy of MPH in the treatment of ADHD, as well as the published algorithms and practice guidelines for using MPH. The experts reviewed the algorithms for practicality and acceptability by clinicians. RESULTS: Algorithms that included MPH commonly selected it as the initial medication to be employed in the treatment of children with ADHD. Factors involved included its high efficacy, good safety record, and the ubiquitous nature of its appearance in the ADHD treatment literature. CONCLUSIONS: MPH should be considered as the first medication to be used in a treatment algorithm for children and adolescents with ADHD.

Adolescent↗

PubMed2000

Methylphenidate affects striatal dopamine differently in an animal model for attention-deficit/hyperactivity disorder--the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) is used as a model for attention-deficit/hyperactivity disorder (ADHD) because it has behavioural characteristics (hyperactivity, impulsiveness, poorly sustained attention) similar to those of ADHD. ADHD children have been shown to have reduced striatal activation in certain tasks. SHR have reduced striatal dopamine release in response to electrical stimulation. The present study set out to investigate possible long-term effects of methylphenidate treatment on dopaminergic function in striatal slices of SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. Methylphenidate treatment (3 mg/kg daily for 14 days) did not normalize the decreased electrically-stimulated release of [(3)H]dopamine from SHR caudate-putamen slices nor did it affect postsynaptic D(2) receptor function. However, the second electrical stimulus caused a relatively greater release of [(3)H]dopamine from caudate-putamen slices of methylphenidate-treated SHR than from vehicle-treated SHR, suggesting that presynaptic mechanisms controlling dopamine release had been altered. Interestingly, [(3)H]dopamine release from WKY caudate-putamen slices in response to D(2) autoreceptor blockade by the antagonist, sulpiride, was selectively increased by methylphenidate treatment. This effect was not seen in SHR possibly because D(2) autoreceptor function had already been up-regulated. The results show that methylphenidate is unable to enhance D(2) autoreceptor function in SHR.

Acetylcholine↗

PubMed2000

Behavioral validation of the spontaneously hypertensive rat (SHR) as an animal model of attention-deficit/hyperactivity disorder (AD/HD).

A good model of a disorder is one that: (a) mimics, although in a simpler form than the full-blown clinical case, the fundamentals of the behavioral characteristics, in this case of people with Attention-Deficit/Hyperactivity Disorder (AD/HD;face validity); (b) conforms with a theoretical rationale for the disorder (construct validity); and (c) is able to predict aspects of behavior, genetics and neurobiology previously uncharted in the clinics (predictive validity). This article discusses the Spontaneously Hypertensive Rat (SHR) and some other putative animal models of AD/HD. It is argued that although other strains and species may be hyperactive and/or show attention deficits following genetic, environmental or pharmacological interventions, the SHR is presently the only strain shown to have the major behavioral symptoms of AD/HD. This does not mean that investigating other models cannot give valuable information.

Animals↗

PubMed1999

Behavioural effects in female rats of postnatal exposure to sub-toxic doses of polychlorinated biphenyl congener 153.

Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that are also present in human tissues and breast milk. Behavioural disturbances have been reported in both children and animals exposed perinatally to PCBs. The present study assessed the behavioural consequences in female rats of postnatal exposure to the di-ortho-substituted 2,2',4,4',5,5'-hexachlorobiphenyl (IUPAC no. 153), which is one of the PCB congeners most frequently detected in human milk. The different groups of mothers were dosed via gavage with 5 mg/kg bodyweight of PCB 153 in corn oil or 5 ml/kg bodyweight corn oil vehicle every second day from day 3 to day 13 after delivery. The exposure did not affect the bodyweight of the dams nor the physical development of the pups. Operant behavioural testing of the female offspring by two different schedules of reinforcement was performed. First, the animals were tested by a multiple schedule with two components: fixed interval (FI) and extinction (EXT), which has proved sensitive in revealing changes in activity level. There were no statistically significant differences in frequency or interresponse times of lever pressing between the PCB-exposed female rats and the controls. These results were in contrast to a previous, analogous study where PCB 153 produced an increased frequency of lever presses during the FI in male rats, indicating a sex-specific behavioural effect of PCB 153. The female offspring was also tested by a conjunctive schedule with two components: variable interval (VI) and differential reinforcement of low rate (DRL). This schedule revealed slower acquisition of time discrimination in the PCB 153-exposed females as compared with the controls. The VI-DRL results showed that PCB 153 may also produce long-lasting behavioural effects in female rats following postnatal exposure through the mother's milk.

Analysis of Variance↗

PubMed1998

Sex differences in operant discrimination behaviour in an animal model of attention-deficit hyperactivity disorder.

The present study was aimed at determining whether the behaviour of the spontaneously hypertensive rat (SHR), an animal model of attention-deficit hyperactivity disorder (ADHD), showed sex differences parallel to those seen in ADHD children. The experimental protocol contained an operant discrimination task, a two-component multiple (mult) 2-min fixed interval (FI) 5-min extinction (EXT) schedule of water reinforcement, a reliable behavioural paradigm for testing activity levels, discrimination behaviour and impulsiveness. The results indicated that both male and female SHRs show some of the most important behavioural traits of ADHD. Both were hyperactive and showed discrimination problems in terms of a behavioural extinction deficit towards the end of the EXT component. Still their behaviour differed markedly, which was probably due to quite different underlying mechanisms. The behavioural characteristics of the female SHRs may be compatible with an attention-deficit interpretation, whereas the behavioural characteristics of the male SHRs may be due to a shorter than normal delay-of-reinforcement gradient. The present study strengthens the position of SHR as an animal model of ADHD for future studies that may elucidate details in the underlying neurobiological deficits and for testing various treatment strategies.

Animals↗

PubMed1998

Chronic L-deprenyl treatment alters brain monoamine levels and reduces impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder.

Effects of chronic L-deprenyl administration on hyperactive behaviour and brain monoamine levels were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. SHR were hyperactive, impulsive and had impaired sustained attention when tested with a multiple 2-min fixed interval (FI) 5-min extinction (EXT) schedule of reinforcement. Even low, 0.25 mg/kg, doses of chronically-administered L-deprenyl reduced the impulsiveness (bursts of responses with short interresponse times) of SHR, without altering the general hyperactivity or the impaired sustained attention. The drug had no effect on WKY behaviour. The levels of noradrenaline (NA), dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT) and their metabolites, measured in neostriatum, nucleus accumbens and frontal cortex, showed that L-deprenyl effectively inhibited monoamine oxidase (MAO) activity. These results suggest that impulsiveness is a behavioural component that may be operating independent of the other components, like hyperactivity and deficient sustained attention, and that can be reduced by chronic MAO-B inhibition with L-deprenyl in this strain of rats. The positive effect of L-deprenyl on impulsiveness is discussed as due either to normalization of an asymmetric dopaminergic activity in the nucleus accumbens, or to a restoration of normal DA function in the prefrontal cortex.

Animals↗

PubMed1998

Differences between electrically-, ritalin- and D-amphetamine-stimulated release of [3H]dopamine from brain slices suggest impaired vesicular storage of dopamine in an animal model of Attention-Deficit Hyperactivity Disorder.

The spontaneously hypertensive rat (SHR) has behavioural characteristics which make it a suitable animal model for Attention-Deficit Hyperactivity Disorder (ADHD). The drugs of choice in the treatment of ADHD are methylphenidate and D-amphetamine. Using an in vitro superfusion system, we showed that both drugs released [3H]dopamine (DA) (and metabolites) from prefrontal cortex, nucleus accumbens and caudate-putamen slices, but methylphenidate was from 7- to 17-fold less potent than D-amphetamine. The similarity in the drug effects on SHR and WKY [3H]DA release is in accordance with the fact that there is no 'paradoxical effect' of psychomotor stimulants on ADHD behaviour. Methylphenidate released significantly less [3H]DA from nucleus accumbens slices obtained from SHR than from their normotensive Wistar-Kyoto (WKY) controls. Electrical stimulation released less [3H]DA from prefrontal cortex and caudate-putamen slices of SHR, while D-amphetamine, in contrast to methylphenidate, released more [3H]DA from prefrontal cortex, nucleus accumbens and caudate-putamen slices of SHR compared to WKY. Inhibition of the DA uptake carrier by low concentrations of methylphenidate increased the electrically-stimulated release of [3H]DA to the same extent in SHR and WKY tissue, suggesting that the DA transporter was not responsible for the differences between SHR and WKY. The present results suggest that SHR may have impaired vesicular storage of DA causing leakage of DA into the cytoplasm, since SHR released less [3H]DA from vesicular stores in response to methylphenidate or electrical stimulation and released more [3H]DA from cytoplasmic stores via the uptake carrier in response to D-amphetamine. Methylphenidate might be the drug of choice in the treatment of ADHD because it releases DA from vesicular stores only and is less potent than D-amphetamine, thus making it possible to adjust the dose and thereby 'normalise' reduced DA function more precisely than is possible with D-amphetamine. There was no difference between SHR and WKY with respect to D-amphetamine-stimulated release of [14C]acetylcholine (ACh) or methylphenidate-induced inhibition of the electrically-stimulated release of [14C]ACh from nucleus accumbens or caudate-putamen slices, suggesting that there is no major change in cholinergic transmission in SHR.

Animals↗

PubMed1998

A quantitative cytochrome oxidase mapping study, cross-regional and neurobehavioural correlations in the anterior forebrain of an animal model of Attention Deficit Hyperactivity Disorder.

The aim of this study was to trace by molecular imaging techniques the neural substrates of attention deficit hyperactivity disorder (ADHD) using the spontaneously hypertensive rat (SHR) as animal model. Adult SHR and Wistar-Kyoto (WKY) controls were used throughout this study. In experiment 1, naive male SHR and WKY were used, whereas in experiment 2 SHR and WKY rats of both genders were trained on a multiple fixed interval (FI (120 s for water, 5-min extinction)) paradigm and sacrificed 6 months later. In both experiments coronal sections of the anterior forebrain were processed for quantitative cytochrome oxidase (COase) histochemistry by the method of Gonzalez-Lima. Optical density values were transformed into actual enzyme activity units by using tissue-calibrated standards. In experiment 1, non-trained male rats of the SHR line showed lower COase activity in the medial and lateral prefrontal cortices, compared with WKY controls. In experiment 2, there was a line x treatment interaction effect in the pole of the nucleus accumbens (ACB). Regional correlative analyses revealed that: (i) under basal conditions, SHR are more synchronized than WKY rats in the COase level of different brain regions; and (ii) the training desynchronizes COase activity in the WKY, further synchronizes it and increases the cross-talk between hemispheres in male SHR only. Neurobehavioral covariations between behavioural scores and metabolic capacity in the medial and lateral prefrontal/frontal cortices, the caudate-putamen complex (CPU), the pole, core, and shell of the accumbal complex (ACB), and the ventral pallidum (VP), indicated that, in the WKY rats, the frequency of lever pressing covaried positively with the COase activity in the CPU, whereas in the SHR covaried with both medial and lateral prefrontal/frontal cortices. The bursts of activity during the 1-1.33-s segment was positively correlated, in the WKY rats only, with the core and shell of the ACB, and with the VP. Finally, the correlative profiles showed significant gender differences with effects in male SHR only. Thus, the results lend support to the involvement of the cortico-striato-pallidal system in ADHD.

Animals↗

PubMed1998

Behavioural hyperactivity in rats following postnatal exposure to sub-toxic doses of polychlorinated biphenyl congeners 153 and 126.

Rats were exposed through mother's milk either to the di-ortho-substituted polychlorinated biphenyl (PCB) congener 2,2',4,4',5,5'-CB (IUPAC no. 153) or to the non-ortho-substituted PCB congener 3,3',4,4',5-CB (IUPAC no. 126). The different groups of mothers were dosed via gavage with corn oil vehicle, 5 mg/kg b.w. of PCB 153 or 2 microg/kg b.w. of PCB 126 every second day from day 3 to 13 after delivery. The exposure did not affect the body weight (b.w.) of the dams or the physical development of the pups. A two-component schedule of reinforcement was used to study behavioural effects of the PCB exposures in male offspring. One component was operating when the house light was turned on. Then a reinforcer, a drop of water, was delivered every 2-min. This component is called a 2-min fixed interval (FI) schedule of reinforcement. The other component was in effect when the house light was turned off. Then no reinforcer was ever delivered. This is called an extinction (EXT) component. It was shown that the PCB-exposed offspring were hyperactive as they had an increased frequency of lever presses. In addition, the PCB 153-exposed male pups showed a behavioural pattern similar to that observed in spontaneously hypertensive rats (SHR), an animal model of attention-deficit hyperactivity disorder (ADHD). This behaviour is characterized by 'burst' of lever presses with short interresponse times (IRT) just before the next reinforcer is given. These results show that both PCBs 153 and 126 may produce significant neurotoxic effects following postnatal exposure through mother's milk.

Animals↗

PubMed1998

Attention deficit/hyperactivity disorder--from brain dysfunctions to behaviour.

This special issue represents an attempt to answer fundamental brain and behaviour issues in attention-deficit hyperactivity disorder (ADHD). The European network on hyperkinetic disorders (Eunethydis) is trying to develop a novel, testable theory of ADHD, giving an account of its causes, its development from brain dysfunctions to behavioural symptoms and co-morbidity and explaining why no current therapy produces long-lasting improvements. The combined insights of the articles presented here suggest that there is no brain damage in ADHD, but hypo-efficient dopamine systems which give rise to neurochemical imbalances. These cause behavioural problems: deficits in sustained attention, overactivity and impulsiveness. Impulsiveness is increasingly being seen as a key characteristic of the disorder. None of these symptoms are necessarily primary, but may be secondary to an underlying deficit in reinforcement processes seen particularly in a greater than normal sensitivity to variations in the timing of stimulus presentation. Other symptoms can also be seen: altered effects of reinforcers, increased behavioural variance and motor co-ordination problems. Medication produces temporary, plastic changes in cellular components like receptors and transduction mechanisms normalising dopamine functions and behaviour. reserved.

Adult↗

PubMed1998

Altered reinforcement mechanisms in attention-deficit/hyperactivity disorder.

The present study tested eight boys with attention-deficit/hyperactivity disorder (ADHD) and 12 normal boys (comparison group), aged 7-12 years, to investigate the hypothesis that ADHD is associated with a steeper and shorter delay-of-reinforcement gradient than is normal. A two-component schedule of reinforcement was used to deliver trinkets or coins as reinforcers in a game-like test. One component was marked by a signal. During this period reinforcers (coins or trinkets) were delivered every 30 s. This component is called a 30-s fixed interval (FI) schedule of reinforcement and measures changes in reactivity to reinforcers. The other component was in effect when the signal was turned off. Then no reinforcer was ever delivered. This is called an extinction (EXT) component and measures primarily sustained attention. The ADHD children gradually developed hyperactivity to a large extent consisting of bursts of responses with short interresponse times (IRTs) during both schedule components. The response bursts not only constituted a substantial portion of the ADHD overactivity, but may well be a key component of the behaviour commonly described as impulsiveness, the key behavioural characteristic of ADHD. In addition, the ADHD children showed behaviour during the extinction component that may well be described as a sustained-attention deficit: initially stopping when the signal was turned off and then resuming responding some time thereafter as if the signal had been turned on again. The comparison group ceased responding during extinction and did not show impulsiveness. The findings were in accordance with a steeper and shorter delay gradient in ADHD.

Attention↗

PubMed1997

Short term storage of samples containing monoamines: ascorbic acid and glutathione give better protection against degradation than perchloric acid.

In order to study the protection of monoamines from degradation during short-time storage, the effect of three different antioxidants on the degradation of dopamine, dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) was analyzed after 5 and 20 h. The results showed that dopamine was still quite stable after 20 h storage at room temperature, but that about 95% of 5-HIAA had disappeared. The best protection against degradation of all three substances was achieved when 15% v/v of a solution containing 1-2 mM ascorbic acid or 40 mM glutathione was added to the sample, resulting in near 100% protection after 20 h. Perchloric acid actually accelerated the degradation of 5-HIAA.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

Reduced CaMKII-positive neurones in the accumbens shell of an animal model of attention-deficit hyperactivity disorder.

THIS study aimed at investigating putative neural substrates of attention-deficit hyperactivity disorder in children using the spontaneously hypertensive rat (SHR) as animal model and the Ca2+/calmodulin-dependent protein kinase II (CaMKII) as a marker in the nucleus accumbens, an interface between limbic and motor systems. In prehypertensive male SHR and Wistar-Kyoto rats image analysis of CaMKII immunocytochemistry showed more positive elements in the shell than in the core, and in the former a lower level in SHR. The data indicate a reduced number of nucleus accumbens modules available for limbic-motor integration revealing putative substrates of the altered attentional and reinforcement mechanisms demonstrated in the SHR and in children with attention-deficit hyperactivity disorder.

Animals↗

PubMed1996

NMDA and non-NMDA sensitive [L-3H]glutamate receptor binding in the brain of the Naples high- and low-excitability rats: an autoradiographic study.

The Naples high-excitability (NHE) and low-excitability (NLE) rat lines, selectively bred for high and low activity in a Làt maze, respectively, are used as an animal model in the study of hippocampal functions. The aim of this study was to investigate the anatomical distribution of N-methyl-D-aspartate (NMDA) and non-NMDA sensitive [3H]glutamate receptor binding by quantitative autoradiography in the brain of the NHE and NLE rats with a randomly bred line (NRB) as controls. Twenty-micron-thick cryostat sagittal sections were incubated at 4 degrees C with 150 nM [L-3H]glutamate alone or in the presence of 100 microM NMDA or 2.5 microM quisqualate (QA). Non-specific binding was determined in the presence of 1 mM of non-labeled glutamate. The sections were exposed to tritium-sensitive films for 3 weeks at 4 degrees C. Quantitative analysis revealed: (1) higher levels of total binding in NHE than in NRB and NLE rats in all areas but the cerebellum; (2) fewer binding sites for both NMDA and QA receptors and larger binding sites for QA receptors in the hippocampus of NLE and NHE rats, respectively; (3) a positive correlation between total binding sites and activity level in a Làt maze in all areas, except the cerebellar molecular layer with NLE < NHE, which was due to differential contribution from NMDA and non-NMDA types. Thus, the brain of the NHE rats shows an imbalance between NMDA and non-NMDA sensitive [L-3H]glutamate receptors.

Animals↗

PubMed1995

Altered dopaminergic function in the prefrontal cortex, nucleus accumbens and caudate-putamen of an animal model of attention-deficit hyperactivity disorder--the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) has been proposed as an animal model for Attention-Deficit Hyperactivity Disorder (ADHD). The behavioural problems of ADHD have been suggested to be secondary to altered reinforcement mechanisms resulting from dysfunction of the mesolimbic and mesocortical dopaminergic systems. The present study therefore investigated whether there are regional differences in dopamine (DA) and acetylcholine (ACh) release and DA D2-receptor function in SHR compared to their normotensive Wistar-Kyoto (WKY) controls. The DA D2-receptor agonist, quinpirole, caused significantly greater inhibition of DA release from caudate-putamen but not from nucleus accumbens or prefrontal cortex slices of SHR relative to WKY. DA D2-receptor blockade by the antagonist, sulpiride, caused a significantly greater increase in DA release from nucleus accumbens slices of SHR compared to WKY suggesting increased efficacy of DA autoreceptors at low endogenous agonist concentrations in the nucleus accumbens of SHR. The electrically-stimulated release of DA was significantly lower in caudate-putamen and prefrontal cortex slices of SHR than in slices of WKY. This could be attributed to increased autoreceptor-mediated inhibition of DA release in caudate-putamen slices but not in the prefrontal cortex. No difference was observed between SHR and WKY with respect to DA D2-receptor-mediated inhibition of ACh release from caudate-putamen or nucleus accumbens slices, suggesting that postsynaptic DA D2-receptor function is not altered in SHR relative to WKY.

Acetylcholine↗

PubMed1995

Alpha 2-adrenoceptor mediated inhibition of [3H]dopamine release from nucleus accumbens slices and monoamine levels in a rat model for attention-deficit hyperactivity disorder.

The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention-deficit hyperactivity disorder (ADHD). The behavioural problems have been suggested to be secondary to altered reinforcement mechanisms in which nucleus accumbens dopaminergic activity plays an important role. Interaction between the noradrenergic and dopaminergic system in the nucleus accumbens has been implicated in the locomotor hyperactivity and impaired discriminative performance of SHR. The present study therefore investigated whether there was any change in the alpha 2-adrenoceptor mediated inhibition of dopamine release from nucleus accumbens slices of SHR in comparison with their normotensive Wistar-Kyoto (WKY) controls. The electrically stimulated release of [3H]dopamine (DA) from nucleus accumbens slices was decreased to a similar extent by UK14,304, an alpha 2-adrenoceptor agonist, in SHR and WKY. Basal norepinephrine (NE) levels were increased in locus coeruleus (LC) and A2 noradrenergic nuclei, but not in the A1 nucleus of SHR, while basal serotonin (5-HT) levels were increased in all these pons-medulla nuclei. These results suggest that a primarily dysfunctional LC and A2 nucleus does not have a secondary effect on dopaminergic transmission in the nucleus accumbens via alpha 2-adrenoceptor mediated inhibition of DA release. Basal monoamine levels in several brain areas of SHR were significantly different from that of WKY. DA, and 5-HT turnover were decreased in SHR versus WKY suggesting hypofunctional dopaminergic and serotonergic systems in some brain areas of SHR.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1993

Spontaneously hypertensive rats (SHR) as a putative animal model of childhood hyperkinesis: SHR behavior compared to four other rat strains.

Childhood hyperkinesis or attention-deficit hyperactivity disorder (ADHD) is a behavior disorder of which the main symptoms are attention problems and hyperactivity. The main objective of the present study was to investigate whether the spontaneously hypertensive rat (SHR) strain is a useful animal model of ADHD. Five different rat strains were tested: SHR, Wistar-Kyoto (WKY), Wistar, Sprague-Dawley (SPRD), and PVG (hooded) rats. The protocol consisted of three different test procedures: 1) A 7.5-min free-exploration open-field test (home cage accessible), where the SHR was less active than Wistar and SPRD but more active than WKY; SHR showed longer latencies to leave the home cage than both Wistar and SPRD rats, spending less time in the field, ambulating and rearing less than Wistar and SPRD but more than WKY. Within session, the SHR tended to be more active at the end of the session than at the start, while the opposite tended to be the case in the other groups. 2) A 7.5-min forced exploration open-field test (home cage not accessible), where the results showed that the SHR is less active than both the Wistar and Sprague-Dawley strains, but more active than PVG and WKY. 3) A two-component multiple schedule of reinforcement with a fixed interval 2 min signalled by houselight on and a 5-min extinction signalled by houselight off. Lever pressing by SHR was markedly different from that of the other four strains, which were quite Except early in the interval, SHR pressed the lever more than any of the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Frequent reward eliminates differences in activity between hyperkinetic rats and controls.

The spontaneously hypertensive rat (SHR) is a strain that is a potential animal model of attention-deficit hyperactivity disorder (ADHD)/childhood hyperkinesis/disturbance of activity and attention, as SHR exhibit both hyperactivity and attention problems. Altered reinforcement (reward) processes have been suggested as the mechanism for the development of hyperactivity in SHR and ADHD. The purpose of the present study was to analyze basic reinforcement and response processes in the hyperactive SHR and in the progenitor Wistar-Kyoto (WKY) control strain. The results show that differences between the strains emerge in response rates maintained by infrequent reinforcers rather than in asymptotic rates of responding maintained by higher rates of reinforcement. The SHR strain required fewer reinforcers per minute to maintain high rates of responding, but when reinforcer rates were high enough to maintain asymptotic response rates in both strains, the rates were similar. Thus, the increased response rates for hyperactive rats at low reinforcement rates may reflect not only barpresses for water, but possibly also barpresses for other stimuli the animal produces by pressing the lever switch. Extrapolating to hyperactive children (ADHD), the results suggest that ADHD behavior might be made more similar to non-ADHD if reinforcers were scheduled more frequently.

Animals↗