Testosterone administration in chicks affects responding in the presence of task irrelevant stimulus changes

Introduction: A series of studies have shown that circulating testosterone increases the persistence with which animals search for and select a particular visual cue to respond to (as a consequence of experience with it) - and hence incur a perseveration of response towards such cues (e.g. Rogers 1971; Andrew 1972, Archer 1976; Earley & Leonard 1978). We tested the effect of testosterone on such attention-related mechanisms by studying the effect of intradimensionsional colour changes to cues relevant and irrelevant to an operant discrimination on continuous reinforcement learning (non-reversal shifts). Methods: Treatment: Chicks (20 males) were given 12.5 mg testosterone enanthate im after training on a continuous reinforcement schedule of response (CRF); 19 controls received sesame oil vehicle and 8 males and 15 females had no treatment. Testing: Birds were given A) test sessions on day 10 and 11: whereby each session consisted of 2 minutes training, 5 minutes test then 2 minutes re-training: B) 4 types of test --(i) the negative key colour changed from red to deep blue, (ii) the positive key colour changed from pale blue to green, and (iii) both key colours changed as described, and (iv) the overhead lighting changed with the introduction of a pale red filter. Results: 1/ Treatment did not affect CRF patterns of discriminative responding. 2/ All birds decreased their response rate after a colour change. 3/ After changes on the non-reinforced key, testosterone treated birds showed significantly less attenuation of response rate. 4/ Testosterone treatment also maintained a higher rate of response (and hence fewer reinforcements) - seen especially after a change in the negative cue or overhead lighting vs. changes in the positive cue (irrelevant changes of stimulation). 5/ Testosterone treated birds also showed a shorter latency to respond after a colour change. 6/ The female birds did not differ from the males Conclusions: The results support a role for testosterone in the discrimination between relevant and irrelevant stimulus changes and the persistent expression of learned sets. The fact that responding after testosterone treatment was altered by irrelevant rather than relevant stimulus changes suggests that testosterone achieves its persistence effect by enhancing the activated set or what is at the focus of attention, rather than the inhibition of features irrelevant to the ongoing situation - these provide the reference for 'what is relevant' and changes in them disturb this mechanis

p-Chlorophenylalanine-produced effects on behavior in intact and brain-damaged rats

Introduction: Our aim was to determine if a reduction of serotonin (5-HT) synthesis in the brain would provide any protection from the behavioral alterations induced by hippocampal brain-damage. The development of open-field activity (5 minute sessions) over two weeks and the acquisition of a passive avoidance task were chosen for study. Methods: There were 3 groups of lesioned rats - those hippocampal aspiration lesions, those with only damage to the neocortex overlying the hippocampus, and a sham-operated group. Half of each group was treated 300 mg/kg p-chlorphenylalanine (PCPA) for 3 successive days to deplete levels of 5-HT and the other half were given the saline vehicle alone. [Hippocampal damage is associated with increased activity in the open field and impaired learning of the step-through passive avoidance response.] Results: 1/ Animals with hippocampal damage became hyperactive in the second week after operation. 2/ PCPA treatment had no effect on locomotion, (nor on the frequently observed thigmotaxic nature of the behavior) 3/ Rearing was initially depressed after the operation, and PCPA treatment facilitated its recovery - but PCPA decreased rearing in intact animals during the second week of testing. 4/ Reduced levels of grooming were seen in hippocampal animals, while PCPA reduced grooming in those with neocortical damage 5/ The animals with hippocampal damage were impaired in witholding response in the passive avoidance task - those treated with PCPA performed even worse in not witholding the shock-reinforced step-through response. This contrasted with the intact animals, where PCPA treatment reduced the amount of footshock the animals were exposed to in the task Conclusions: .The results are consistent with a role for mesolimbic 5-HT innervation of the dorsal hippocampus having an influence on novelty-elicited responses (e.g. grooming in home vs. novel cage and investigative rearing behavior) and in modulation of the sensitivity of response to electric footshock (hypersensitive in PCPA-intact animals, hyposensitive in PCPA-hippocampal animals)

Frontal, temporal and lateralized brain function in children with attention-defiocit hyperactivity disorder: a psychophysiological and neuropsychological viewpoint on development

Introduction: This review considers deficits in the selective aspects of perception (i.e. attention) underlying symptoms of impaired attention and impulsivity in children with attention-deficit hyperactivity syndrome (ADHD) in terms of frontal and temporal lobe function and cerebral asymmetry. Review: Tomographic studies suggest a disturbance of fronto-striatal function, but have neglected limbic contributions under activating conditions and are contradictory or equivocal on the nature of apparent lateralised differences of structure. Functional neuropsychological (e.g. go/no-go and covert orienting of attention tasks) and psychophysiological studies (e.g. event-related potentials and mismatch negativity [1]) suggest that early and late stages of information processing are affected in both the frontal and temporal lobes. Performance differences in young ADHD patients imply an impairment in the inter-cortical dialogue. Given the evidence for a normal specialisation in global processing in the right and the processing of details in the left hemisphere, the lateralised impairment may progress from situational ADHD (resulting in impaired selective aspects of perception on the right) to pervasive ADHD (inducing an additional impairment in decision making on the left: compare risk taking). Conclusions: Accordingly a proportion of ADHD children may experience an early negative neurodevelopmental influence that only appears as the brain region matures (especially around 8-12 years of age) while others show an independent, longer term, delayed development of CNS function

The role of noradrenaline in tuning and dopamine in switching between signals in the CNS

Introduction- Thesis: Neuronal catecholaminergic activity modulates central nervous (CNS) function. - Specifically - Noradrenaline (NA) can exert a tuning or biassing function, whereby the signal-to-noise ratio is altered. Dopamine (DA) activity may promote switching between inputs and outputs of information to specific brain regions. Background: It has been ten years since evidence for a tuning function was advanced for NA (Segal & Bloom, 1976 a, b), and in the last five years the switching hypothesis for DA has been tentatively put forward (Cools, 1980). Review: Recent studies are reviewed to show that while catecholamine activity contributes to neural interactions in separate brain regions, that give rise to the organization of different functions, their working principles may be common between species and independent of the nucleus of origin. Behavioral examples are discussed and an attempt is made to integrate this with evidence from intracellular recording studies. It is suggested that the tuning principle in NA systems is particularly important for the formation of associations and neural plasticity (interference control), and that the switching principle of DA systems modulates the timing, time-sharing and initiation of responses (program-control)

Attention deficit disorder and hyperkinetic syndrome: biological perspectives

The condition, biological indicators and animal models of the symptoms and the disorder are briefly reviewed. Condition: No single symptom is indispensable to diagnosis. But measures of the condition include motor activity, attention, motivation and psychostimulant responsiveness.Caveat: In the study of the condition, measuring biological correlates of unusual function may prove useful for management of the condition, but could mislead in the search for causes. Biological indicators: Investigation of attention-related function and associated regional cerebral activity would be improved by the careful application of the results of neuropsychological and psychophysiological study. A more extensive use of within subject protocols would greatly assist interpretation of the relevance of physiological states and the contribution of activity in different transmitter systems.Why are MHPG levels low, and lower in stimulant responders: HVA/MHPG ratios high in responders and nonresponders alike? However, the author sees the paradox to lie less with the induced (sic) metabolic changes as with the inability to mimic the changes with other catecholaminergic agents. Attention is drawn to the trophic effects of the monoamines. Attention is also drawn to the colocalisation of neuropeptide Y in NA neurons and the possibility that alterations in this relationship could underlie other ADHD characteristics such as thirst (1). Models: Symptom-models attempt to investigate the determinants a single feature of the illness. Examples have been recent demonstrations that where NA activity is low or depleted selective attention may be impaired (e.g. latent inhibition). An interesting observation here is that where NA activity is low, learning in a variety of situations occurs at normal rates to a modest criterion, but then slows severely before eventually reaching good stringent criteria. It is suggested that this is consistent with an NA role in "tuning" (2).Discussion of the various roles of DA must make mention of the specific improvement seen after amphetamine treatment in those children who only achieve a low response criterion: in contrast in animals amphetamine promotes the impulsive response lowering beta-criterion. The resolution oif the enigma may well lie in a better understanding of the interactions of the mesolimbic with the mesocortical DA system. Mesocortical activity can suppress mesolimbic activity, impairment of frontal function releases the mesolimbic system - a change that can be countered by psychostimulant treatment. Disorder-models are concerned with mimicking a whole cluster of symptoms if not the syndrome itself. Claims of the usefulness of depleting catecholamines with 6-hydroxydopamine (on the one hand) and modifying the environment in which young animals are brought up (rich andsocial contexts for development) are elaborated elsewhere in this book. The similarity of some of the features of hypertensive patients and those of youngsters with ADHD initiates interest in the "spontaneously hypertensive rat" (SHR). Encouraging the use of the SHR as a model are similarities in the DA and NA activity and reactivity. Further, there are similarities in between the responses of the SHR and children on learning schedules requiring the delay of response, - the delay of gratification that is characteristic of many ADHD children, and leads to impulsive responding in the SHR. Lastly one should not overlook the possible lessons to be learned in the comparative approach, - namely to look at syndromes with more or fewer comorbid symptoms such as Tourette, Conduct-Disorder, Autism, Lesch.Nyhan and Phenylketonuria (3)

Plasma neuropeptide-Y levels, monoamine metabolism, electrolyte excretion and drinking behavior in children with attention-deficit hyperactivity disorder

Introduction: This study was conducted against a background of the following four points: a) increased drinking behavior in children with attention-deficit hyperactivity disorder (ADHD), b) the parallel between some behaviours associated with ADHD and with hypertension, c) the use of the spontaneously hypertensive rat as a model for ADHD, and d) similarities in the changes of neuropeptide-Y (NPY) and catecholamine in the studies of hypertension and drinking, Methods: Measures of NPY, catecholamines and electrolyte balance were compared in the plasma and urine of healthy children and those with ADHD. Drinking was monitored during three hours of neuropsychological tests over two days in 14 ADHD (mean 9.8 years-of-age) and 9 healthy children (10.6 years-of-age). Results: Patients drank 4 times more water and showed twice the levels of NPY in controls. In controls there were positive and in patients there were negative relationships for NPY with drinking and restless behavior. Patients' plasma levels of norepinephrine (NE) and epinephrine were slightly elevated, but urinary levels of NE and the serotonin metabolite were markedly increased. Urinary excretion rates for sodium (not potassium), phosphate and, especially calcium were decreased in patients. NPY levels were inversely related to calcium excretion and drinking inversely to sodium circulating (but positively with potassium and phosphate excretion). Conclusions: Increases of drinking and increased levels of circulating NPY in ADHD children and decreased electrolyte excretion may reflect a common disturbance in the homeostatic control of metabolism.This may contribute to the impairments of attentional and behavioural control typical of ADHD children

Event-related potentials in autistic and healthy children on an auditory choice reaction time task

Introduction: Childhood autism can occur in 5 out of 10,000 of the population. The condition covers problems of sensory modulation, comprehension and communication as it relates to both objects and people. Of the stages of information processing recorded in auditory event-related potentials (ERPs), reductions of N1 and P3 amplitude have been reported in many situations, but an increased P3 response to non-targets may represent difficulties in attributing differentially significance to some but not all stimuli.. Methods: Recordings were derived from midline and 4 lateral sites on the scalp of 7 children with autism and 7/13 healthy control children matched for age (median 139 vs. 135 months). A three-tone oddball paradigm was presented in a passive and active-task form (72% at 1 kHz, 14% at 0.5 kHz and 14% at 2.0 kHz) Results: a) Autistic subjects showed twice as many errors of omission and a higher beta criterion (signal detection) for targets. b) For autistic subjects N1 latencies were shorter and N1 amplitude larger to deviants (especially nontargets). c) However, subtraction of the ERPs in nontarget from target conditions showed that the processing negativity (PN) and especially the Negative difference (Nd) was smaller in autistic subjects. d) In contrast the P3 amplitude (especially after the target) was smaller in autistic subjects. e) Within autistic subjects the topography showed more early negativity after deviants at left frontal sites and more target induced late positivity at right parietal sites. Conclusions: The ERPs of autistic children were more responsive to stimulus features (high frequency or deviance) and less responsive to the stimulus associations (target features). The ERPs also provide conflicting signs of neurodevelopment, -- precocious in the right-hemispheric emphasis for P3, but delayed in that P3 was not maximal at parietal sites

Dopamine-sensitive alternation and collateral behaviour in a Y-maze: effects of d-amphetamine and haloperidol

Introduction: The frequency of spontaneous alternation in a Y-maze (visiting each arm in turn at p>50%) depends on the influence of the attention given to intra- and extra-maze cues. We examined the observing responses shown by rats (collateral rearing and head-turning behaviour), the habituation to the novelty and alternation responses over 15 minutes/day, four days in a row - in a Y-maze under enhanced and reduced dopamine (DA) activity (amphetamine- and haloperidol treatment). Methods: Prior to placement in a Y-maze for 15 minutes observation on 4 successive days animals were treated with either amphetamine (0.5 or 2.5 mg/kg) or pre-treated with a low dose of haloperidol (0.08 mg/kg, ip). Results: 1/ Amphetamine treated animals chose the arms at random on day 1, but after the higher dose on day 2-4 they perseverated their choice. The controls maintained their alternation over this period. 2/ The amphetamine-induced effects on alternation were prevented by prior treatment with the neuroleptic haloperidol. 3/ Amphetamine treatment increased the frequency of rearing in the middle at the choice point of the Y-maze. Haloperidol pre-treatment blocked this increase at the midpoint on day 1, and blocked the rearing behavior at the end of an arm on day 2. 4/ Amphetamine also increased the frequency of head turning and "looking", - an effect that was also prevented by haloperidol. (day 2 onwards). 5/ Haloperidol increased the duration of" looking" and of rearing at the end of an arm later in testing.. Conclusions: Two effects are postulated to have occurred. a) a conflict on day 1 between the novelty-controlled sensory or attentional effects, that leads to an alternation of arm-choice, and amphetamine-induced DA activity that facilitates an alternation of behavioural responses: -- the result was random choice and increased rearing at the choice point. b) On days 2-4 the drug-induced effects on switching motor responses came to control behaviou

Ventral tegmental (A10) system: neurobiology. 1. anatomy and connectivity

Introduction: The VTA contains the A 10 group of dopamine (DA) containing neurons. These neurons have ben grouped into nuclei to be found on the floor of the midbrain tegmentum - the Nucleus paranigralis (Npn), Nucleus interfasicularis (Nif), Nucleus parabrachialis (Npbp) and the Nucleus linearis (rostralis and caudalis) *. The VTA is traversed by many blood vessels and nerve fibers **. Close to its poorly defined borders are found DA (A8, A9, A11) and 5-HT containing neurons (B8). * Figures 2-4 show electron micrographs and drawings ** Figure 6 , electronmicrographs show neurovascular contacts in the rat and cat that could be used for, say, steroid hormone influence on neurotransmission. Efferent projections of the VTA can be divided into 5 subsystems. The mesorhombencephalic projects to other monoaminergic nucei, the cerebellum and a fine projection descends to other tegmental nuclei as far as the inferior olive. Fibers to the spinal cord havenot been demonstrated. The mesodiencephalic path projects to several thalamic and hypothalamic nuclei andpossibly the median eminence. Functionally important examples are the anterior hypothalamic-preoptic area, Nucleus medialis dorsalis and reuniens thalami. These two subsystems are largely non-dopaminergic. A minor mesostriatal projection is overshadowed by the large mesolimbic projection to the Nucleus accumbens, Tuberculum olfactorium, Septum lateralis and Nucleus interstitialis stria terminalis. There are also mesolimbic connections with several amygdaloid nuclei (especially centralis and basolateralis), the olfactory nuclei and Entorhinal cortex. A minor projection to the hippocampus has been detected. The mesocortical pathway projects to sensory (e.g. visual) motor, limbic (e.g. retrosplenial) and polysensory association coretices (e.g. prefrontal). Prefrontal, orbitofrontal (insular) and cingulate cortices receive the most marked innervation from the VTA. A more widespread presence of DA in other cortices of rodents becomes progressively more evident in carnivores and primates. Most but not all projections are unilateral (see Table VI for % crossed). Some neurons project to more than one area in mesodiencephalic, limbic and cortical systems. The majority of these fibers ascend in the medial forebrain bundle (MFB). Most areas receiving a projection from the VTA (DA or non-DA) project back to the VTA. The septo-hippocampal complex in particiular and the limbic system in general provide quantitatively much less feedback than other areas. The role of the VTA as a mediator of dialogue with the fronto - striatal and limbic / extrapyramidal system is discussed under the theme of " circuit " systems (Figure 11, 12 & 13). The large convergence of afferents to certain VTA projection areas (e.g., prefrontal, entorhinal cortices, lateral septum, central amygdala, habenula, and N. accumbens) is discussed under the theme of " convergence " systems (Figure 15 & 16). Animal studies clearly demonstrate that the VTA in general, and its DA projections in particular are strategically organized to influence integrative neural function in diverse regions of the meso-, di- and telencephalon