Response Stereotypy Research Articles

The role of CYP2D in rat brain in methamphetamine-induced striatal dopamine and serotonin release and behavioral sensitization

RationaleCytochrome P450 2D (CYP2D) enzymes metabolize many addictive drugs, including methamphetamine. Variable CYP2D metabolism in the brain may alter CNS drug/metabolite concentrations, consequently affecting addiction liability and neuropsychiatric outcomes; components of these can be modeled by behavioral sensitization in rats.MethodsTo investigate the role of CYP2D in the brain in methamphetamine-induced behavioral sensitization, rats were pretreated centrally with a CYP2D irreversible inhibitor (or vehicle) 20 h prior to each of 7 daily methamphetamine (0.5 mg/kg subcutaneous) injections. In vivo brain microdialysis was used to assess brain drug and metabolite concentrations, and neurotransmitter release.ResultsCYP2D inhibitor (versus vehicle) pretreatment enhanced methamphetamine-induced stereotypy response sensitization. CYP2D inhibitor pretreatment increased brain methamphetamine concentrations and decreased the brain p-hydroxylation metabolic ratio. With microdialysis conducted on days 1 and 7, CYP2D inhibitor pretreatment exacerbated stereotypy sensitization and enhanced dopamine and serotonin release in the dorsal striatum. Day 1 brain methamphetamine and amphetamine concentrations correlated with dopamine and serotonin release, which in turn correlated with the stereotypy response slope across sessions (i.e., day 1 through day 7), used as a measure of sensitization.ConclusionsCYP2D-mediated methamphetamine metabolism in the brain is sufficient to alter behavioral sensitization, brain drug concentrations, and striatal dopamine and serotonin release. Moreover, day 1 methamphetamine-induced neurotransmitter release may be an important predictor of subsequent behavioral sensitization. This suggests the novel contribution of CYP2D in the brain to methamphetamine-induced behavioral sensitization and suggests that the wide variation in human brain CYP2D6 may contribute to differential methamphetamine responses and chronic effects.

Antioxidant Treatment with N-acetyl Cysteine Prevents the Development of Cognitive and Social Behavioral Deficits that Result from Perinatal Ketamine Treatment.

Alterations of the normal redox state can be found in all stages of schizophrenia, suggesting a key role for oxidative stress in the etiology and maintenance of the disease. Pharmacological blockade of N-methyl-D-aspartic acid (NMDA) receptors can disrupt natural antioxidant defense systems and induce schizophrenia-like behaviors in animals and healthy human subjects. Perinatal administration of the NMDA receptor (NMDAR) antagonist ketamine produces persistent behavioral deficits in adult mice which mimic a range of positive, negative, and cognitive symptoms that characterize schizophrenia. Here we tested whether antioxidant treatment with the glutathione (GSH) precursor N-acetyl-cysteine (NAC) can prevent the development of these behavioral deficits. On postnatal days (PND) 7, 9 and 11, we treated mice with subanesthetic doses (30 mg/kg) of ketamine or saline. Two groups (either ketamine or saline treated) also received NAC throughout development. In adult animals (PND 70–120) we then assessed behavioral alterations in a battery of cognitive and psychomotor tasks. Ketamine-treated animals showed deficits in a task of cognitive flexibility, abnormal patterns of spontaneous alternation, deficits in novel-object recognition, as well as social interaction. Developmental ketamine treatment also induced behavioral stereotypy in response to an acute amphetamine challenge, and it impaired sensorimotor gating, measured as reduced prepulse inhibition (PPI) of the startle response. All of these behavioral abnormalities were either prevented or strongly ameliorated by NAC co-treatment. These results suggest that oxidative stress is a major factor for the development of the ketamine-induced behavioral dysfunctions, and that restoring oxidative balance during the prodromal stage of schizophrenia might be able to ameliorate the development of several major symptoms of the disease.

CRF1 receptor-deficiency increases cocaine reward

Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF1 receptor-deficient (CRF1-/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF1-/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF1-/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF1-/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF1-/- mice by exogenous corticosterone does not affect CRF1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF1 receptor in cocaine reward, independently of the closely related HPA axis activity.

Impaired cognitive functioning in cervical dystonia

Event Abstract Back to Event Impaired cognitive functioning in cervical dystonia Tobias Loetscher1*, Michelle McDonnell2 and Lynley Bradnam3 1 Flinders University, School of Psychology, Australia 2 University of South Australia, School of Health Sciences, Australia 3 Flinders University, School of Medicine, Australia Cervical dystonia is a movement disorder characterized by involuntary muscle contractions that cause abnormal postures of the head and neck. Current research suggests that impairments in a widespread network involving the basal ganglia and cerebellum underlie the disorder. Interestingly, evidence for cognitive dysfunctions associated with dystonia is limited. To further elucidate cognitive functioning in dystonia we employed a random number generation (RNG) paradigm. RNG is thought to be a demanding task that taps into working memory and the executive processes of the brain. Ten patients with cervical dystonia and 40 age-matched controls were asked to name 66 numbers ranging between 1 and 6 in a sequence as random as possible. Patients demonstrated an enhanced response stereotypy (Evans RNG index, t=3.1, p=0.003) and difficulties in supressing habitual responses (counting bias, t=2.7, p=0.01) when RNG performance was compared to the controls. The cognitive impairments were not related to measures of disability and pain (Toronto Western Spasmodic Torticollis Rating Scale). This study adds to the small, but growing number of literature indicating the presence of cognitive deficits in dystonia. The observed pattern of RNG deficits in people with cervical dystonia is similar to the one found in patients with other movement disorders associated with fronto-striatal abnormalities (Parkinson's and Huntington's disease). Understanding cognitive deficits in cervical dystonia may help to elucidate the neural contributions to dystonia that remain elusive and limit the development of effective treatments. Keywords: Dystonia, Movement Disorders, working memory, executive processes, Random Number Generation Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Cognition and Executive Processes Citation: Loetscher T, McDonnell M and Bradnam L (2015). Impaired cognitive functioning in cervical dystonia. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00271 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Dr. Tobias Loetscher, Flinders University, School of Psychology, Adelaide, Australia, tobias.loetscher@unisa.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Tobias Loetscher Michelle McDonnell Lynley Bradnam Google Tobias Loetscher Michelle McDonnell Lynley Bradnam Google Scholar Tobias Loetscher Michelle McDonnell Lynley Bradnam PubMed Tobias Loetscher Michelle McDonnell Lynley Bradnam Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Establishing the Reliability of Word Association Data for Investigating Individual and Group Differences

This article argues that, across different psychological contexts, the methods of data collection, treatment, and analysis in word association tests have hitherto been inconsistent. We demonstrate that this inconsistency has resulted from inadequate control, in previous studies, of certain important variables including the basis of norm comparisons, and we present a principled method for collecting, scoring, and analysing association responses, to address these issues. The method is evaluated using test and retest data sets from 16-year-old and over65-year-old twins (n = 636), which enable us to (a) compare samples matched for key environmental variables, (b) assess the transferability of norming information between age cohorts, and (c) evaluate the reliability of the scoring protocols. We find systematic differences in the association behaviour of the two age cohorts, indicating the importance of evaluating data only against norms lists that are matched to the target population. Individual association behaviour is found to be consistent across test times, both in terms of response stereotypy and response type.

Radial-arm-maze behavior of the red-footed tortoise (Geochelone carbonaria).

The radial-arm maze is an established method for testing an animal's spatial win-shift behavior. Research on mammals, birds, and fish has shown that the mastery of this task is commonly mediated, to different degrees, by two types of strategy: those based on external cues and those based on response stereotypy. In the present study we trained four red-footed tortoises (Geochelone carbonaria) to navigate an eight-arm radial maze while providing different levels of access to visual room cues. The results indicate that response stereotypy is the more prevalent mechanism in these tortoises, although navigation based on landmarks can also occur if learned initially. The findings suggest that tortoise spatial navigation may be more similar to that observed in mammals and birds than previously thought.

Applying Psychophysiological Measures to Marketing and Advertising Research Problems

Abstract Applications of psychophysiological measures to the problem of evaluating advertising and marketing stimuli are reviewed. It is suggested that most of these applications have been simplistic and based on the erroneous concept of a unitary activation continuum. Fundamental principles of psychophysiology have routinely been ignored in such applications. Among these principles are (1) the law of initial values, (2) individual response stereotypy, (3) stimulus-response specificity, and (4) directional fractionation of response. Methodological controls which should be observed when using psychophysiological measures are reviewed. While it is concluded that psychophysiological measures are not a ready solution for problems related to the evaluation of the relative efficacy of marketing and advertising stimuli, certain applications of psychophysiological measures to marketing and advertising research appear viable.

The role of the dopamine transporter DAT1 genotype on the neural correlates of cognitive flexibility

Cognitive flexibility, the ability to adapt goal-oriented behaviour in response to changing environmental demands, varies widely amongst individuals, yet its underlying neural mechanisms are not fully understood. Neuropharmacological and human clinical studies have suggested a critical role for striatal dopaminergic function mediated by the dopamine transporter (DAT). The present study aimed at revealing the role of the DAT in the individual brain response stereotypy underlying cognitive flexibility. A task-switching protocol was administered to a sample divided according to the presence or absence of the 9-repeat (9R) allele of the DAT1 polymorphism, while registering behavioural and electrophysiological novelty-P3 responses. The absence of the 9R (higher gene expression) is related to less striatal DA availability. Individuals lacking the 9R (9R-) showed specific response time (RT) increases for sensory change and task-set reconfiguration, as well as brain modulations not observed in participants with the 9R allele (9R+), suggesting that task performance of the former group depended on immediate local context. In contrast, individuals displaying high striatal DA showed larger RT costs than 9R- individuals to any sensory change, with no further increase for task-set reconfiguration, and a larger early positive brain response irrespective of the task condition, probably reflecting larger inhibition of any previous interference as well as stronger activation of the current task set. However, the polymorphic groups did not differ in their mean RTs in trials requiring task-set reconfiguration. This distinct stereotypy of cerebral responses reveals different patterns of cognitive control according to the DAT1 gene polymorphism.

Random number generation in neglect patients reveals enhanced response stereotypy, but no neglect in number space

Based on interactions between number and space apparent from healthy subjects’ randomization attempts we expected random number generation (RNG) to be sensitive for the monitoring of unilateral spatial deficits. Specifically, we predicted patients with left-sided hemineglect to evidence “neglect in number space”, i.e. to produce a deficiency in the generation of small, “left-sided” numbers. In RNG of digits from 1 to 6, 19 patients with left-sided neglect generated sequences with a higher redundancy, but as many small numbers as did a matched control group. We discuss possible reasons for the absence of a small-number neglect and emphasize that the observed redundancy was not due to a counting bias, as known from other neurological patients, but to an unspecific imbalance in the use of response alternatives. We speculate that this may be the consequence of disrupted fronto-parietal functions normally serving in the sequential organization and manipulation of items in working memory.

Autonomic Stress Response Modes and Ambulatory Heart Rate Level and Variability

The major goals of this study were (1) to determine consistency of autonomic response modes to different laboratory stressors, and (2) to evaluate the strength of the association between autonomic response modes and ambulatory heart rate and variability. The sample consisted of 45 healthy participants. Parasympathetic (PNS) and sympathetic (SNS) reactivity to and recovery from laboratory stressors (handgrip, logical-mathematical, mirror-tracing, and rumination tasks) were estimated by high frequency heart rate variability (HF-HRV), preejection period (PEP), and baroreflex sensitivity (BRS). Ambulatory HR was measured for 24 h on a work and a nonwork day, counterbalanced. As BRS was less reliable compared to PEP and HF-HRV, the latter two parameters were selected for the computation of SNS/PNS patterns. Autonomic modes were consistent across tasks and more stable during the recovery periods. Moreover, recovery appeared to be sensitive to the emotionality of tasks. Reactivity and recovery patterns differed as a function of gender, with women showing higher vagal tone at baseline, higher HR reactivity to the logical task, greater BRS decrease during the rumination task, and a larger decrease in vagal tone during recovery after the rumination task. After controlling for gender and baseline HR and variability, autonomic profiles during reactivity and recovery periods captured substantially different ambulatory information. Specifically, autonomic profiles during reactivity significantly predicted ambulatory HR level during waking hours, whereas autonomic profile during recovery was linked with ambulatory HRV. Coactivation of SNS and PNS activity was associated with the highest ambulatory HR levels and variability. Findings from the laboratory were consistent with a dimensional autonomic model viewing SNS and PNS contributions to heart rate on orthogonal axes and individual stress response stereotypy. Laboratory task-related autonomic reactivity and recovery may reflect parallel differences in HR level and variability in everyday life.

Chronic benzylpiperazine (BZP) exposure produces behavioral sensitization and cross-sensitization to methamphetamine (MA)

Background Like other psychostimulant drugs, acute exposure to benzylpiperazine (BZP) increases dopaminergic neurotransmission, producing hyperactivity and stereotypy. The consequences of repeated BZP exposure have not however been investigated. The effects of acute and repeated BZP and methamphetamine (MA) exposure on locomotor activity and stereotypy were measured in order to determine whether there was sensitization and cross-sensitization between these two psychostimulant drugs. Methods The effects of acute treatment with MA (0.0, 0.5, 1.0 and 2.0 mg/kg, intraperitoneal (IP)) or BZP (0.0, 5.0, 10.0, 20.0 and 40.0 mg/kg, IP) on locomotor activity and stereotypy were determined. Effects of repeated exposure were determined in other groups that received five daily injections of 2.0 mg/kg MA, 20.0 mg/kg BZP or vehicle. Following a 2-day withdrawal period, rats from each treatment group received either a low dose MA (0.5 mg/kg) or BZP (10.0 mg/kg). Results MA and BZP produced dose-dependent hyperactivity and stereotypy. Repeated MA and BZP resulted in a potentiated locomotor but not stereotypy response. Following the withdrawal period, MA pretreated rats exhibited a sensitized locomotor and stereotypy response to the low dose MA and a conditioned response to saline. BZP pretreated rats also demonstrated a sensitized locomotor response to the low dose of BZP and MA. Conclusions The present findings indicate that repeated exposure to BZP results in sensitization and cross-sensitization to MA.

Differential Regulation of Immediate-Early Gene Expression in the Prefrontal Cortex of Rats with a High vs Low Behavioral Response to Methamphetamine

Methamphetamine (METH) administration mimics many of the symptoms of mania and can produce psychosis after chronic use. Both rodents and man display interindividual variation in response to METH. The molecular mechanisms underlying these differences might be relevant to both stimulant addiction and endogenous psychosis. We treated 50 Sprague-Dawley rats acutely with METH (4.0 mg/kg) and 10 control rats with saline, and measured their behavior for 3 h after drug administration. Animals were divided into high responders (HR) (top 20%) and low responders (LR) (lowest 20%) based on their stereotypy response. They were killed 24 h after injection. Total RNA was extracted from the prefrontal cortex (PFC) and the expression of approximately 30 000 transcripts were analyzed using Affymetrix 230 2.0 GeneChips. Real-time reverse transcription-polymerase chain reaction was used to validate the expression of a select group of genes. Forty-three genes exhibited significant differences in expression in HR vs LR 24 h after METH treatment including a group of immediate-early genes (IEGs) (eg, c-fos, junB, NGFI-B, serum-regulated glucocorticoid kinase). These IEG expression differences were accompanied by the significant downregulation of many of these genes compared to saline in the HR but not LR, suggesting a differential responsiveness of signal transduction pathways in these two groups of rats. In addition, the expression of other transcription factors in the PFC was significantly different in HR compared to LR. These gene expression changes may contribute to individual differences in responsiveness to stimulants and the development of mania and psychosis.

Cardiovascular Measures of Attention to Illusory and Nonillusory Visual Stimuli

This study was an extension of the Berntson, Cacioppo, and Fieldstone (1996) study that found that attending to visual illusions presented with text (usually a question directing attention to the illusory property) lengthened heart period via uncoupled vagal activation. Eighty participants were assigned to one of four groups that received either the original Berntson et al. illusions or a modification formed by the factorial combination of whether the illusion and its related text were present or absent. Participants also performed the same serial-subtraction mental-arithmetic task from Berntson et al. During the mental-arithmetic task heart period (HP) shortened, respiratory sinus arrhythmia (RSA) was reduced, and preejection period (PEP) shortened, which indicated a reciprocally coupled sympathetic activation and parasympathetic inhibition mode of cardiac control. Although idiographic analyses found this to be the most common control mode, all other modes were also obtained – especially the nonreciprocal modes of coactivation and coinhibition. During the visual task, PEP lengthened for all groups indicating uncoupled sympathetic inhibition while attending to the stimuli; however, HP differed depending upon the illusion factor. HP lengthened when illusions were absent, but unlike Berntson et al. it shortened when illusions were present. Idiographic analyses found that although most participants showed sympathetic inhibition, approximately equal numbers of participants showed parasympathetic activation and inhibition. Variation in response stereotypy may mask cardiac responses elicited by subtle cognitive phenomena such as the processing of visual illusions, especially in passive viewing tasks. We also suggest that individual differences in mental effort needed to integrate top-down and bottom-up perceptual processes, or personality variables such as the need for cognition, may contribute to response variability in the visual task.

Effects of a Synthetic Predator Odor (TMT) on Freezing, Analgesia, Stereotypy, and Spatial Memory

Exposing rats to the predator odor of trimethylthiazoline (TMT), obtained from the red fox, was compared to exposure to the novel control odor of citronella. In E)(periment 1, TMT produced defensive freezing and an analgesic reaction that was reversed by an opiate antagonist. In Experiment 2, TMT augmented response stereotypy induced by an amphetamine injection. In Experiment 3, TMT interfered with working memory during 30-s, but not O-s, delay trials of a spatial-alternation task. However, a larger amount of TMT disrupted performance during delay and no-delay trials. In Experiment 4, TMT impaired the recall of the location of a hidden platform in a Morris water maze, and a preexposure injection of a benzodiazepine agonist prevented this deficit. These findings and their implications are discussed in terms of research involving similar paradigms with other stressors.

Defensiveness and individual response stereotypy in asthma.

Previous literature has shown that the psychological trait of defensiveness is related to elevated sympathetic reactivity to stress and to several cardiac risk factors. The aim of this study was to examine whether these previous findings on defensiveness extend to an asthmatic population. Defensiveness was measured by the Marlowe-Crowne Social Desirability Scale using a quartile split: high (upper 25%) and low (bottom 75%). Twenty-two defensive and 66 nondefensive participants with asthma were exposed to laboratory tasks (initial baseline rest period, reaction time task, and a shop accident film). During the tasks there was evidence of lower skin conductance levels and greater respiratory sinus arrhythmia amplitudes among defensive patients with asthma. After exposure to the tasks, defensive patients with asthma showed a decline on spirometry test measures compared with nondefensive asthmatic patients, who displayed an increase. These data confirm individual response stereotypy and suggest that defensiveness may be characterized by sympathetic hypoarousal and parasympathetic hyperarousal among patients with asthma. Future studies are needed to determine whether defensiveness is a risk factor for stress-induced bronchoconstriction.

Apomorphine susceptibility and animal models for psychopathology: genes and environment.

Many years ago we found a bimodal distribution of a number of different behaviors in our regular outbred Wistar stock. This was observed in the response to novelty, the response in a resident-intruder test as well as in the stereotypy response to the dopamine agonist apomorphine. On the basis of that, we decided to selectively breed these animals, which resulted in the the APO-SUS and APO-UNSUS lines. The APO-SUS rats show a strong, stereotyped gnawing response, whereas APO-UNSUS show only a weak gnawing response. Follow-up studies have shown that the phenotypical expression of these rats depend on genetic and early and late environmental factors. Because these rats were not selected on the basis of a specific behavioral trait, but rather on the basis of a difference in susceptibility for a specific neurotransmitter, it is not surprising that these animals show major differences in the neurochemical state of the central nervous system. In fact, in many respects they represent mirror images of each other. Moreover, these animals show clear differences in their endocrine and immunological systems. APO-SUS rats can be characterized as having a hyper-reactive hypothalamus-pituitary-adrenal axis, and a dominance of the T(H2) system. Apart from discussing the main differences between APO-SUS and APO-UNSUS rats, the review specifically focuses on the former as a potential model for schizophrenia. We have been able to show that APO-SUS rats indeed share a large number of behavioral, neurochemical, endocrinological, and immunological similarities with patients suffering from schizophrenia. Because schizophrenia is also likely to result from an interaction between genetic and early stressful life events, the APO-SUS rat might represent a promising animal model for studying this severe mental disorder.

Nomifensine-induced c-fos mRNA expression in discrete brain areas of the developing rat

In rats, the subcutaneous injection of a dopamine uptake inhibitor, nomifensine (40 mg/kg), induced a significant increase in the c-fos mRNA levels in the neocortex on postnatal days 23 and 49, in the striatum on days 8, 14, 23 and 49, and in the hippocampus on day 23, when compared with saline administration. The repeated injection with nomifensine (40 mg/kg once daily) from postnatal days 49 to 53 and from 23 to 27, but not from days 8 to 12 and 14 to 18, resulted in an enhanced stereotypy response elicited by a subsequent challenge of the drug (5 mg/kg) 21 days after the last injection (behavioral sensitization). The present results suggest that the neuronal circuits regulated by nomifensine might undergo regionally-different developmental changes, which could be implicated in the development of behavioral expressions including nomifensine-induced stereotypy sensitization.

Patterns of sympathetic and parasympathetic reactivity in a sample of children and adolescents

We hypothesized that patterns of sympathetic and parasympathetic reactivity observed in adults would be apparent in a sample of children and adolescents and that these patterns would be consistent across tasks. We explored the relationship between these patterns and psychosocial risk factors for cardiovascular disease. We measured preejection period (PEP) and an index of respiratory sinus arrhythmia (mean successive difference [MSD] statistic) during three reactivity tasks. We classified participants into four groups based on increases or decreases in PEP and MSD. Ninety percent of the sample exhibited the same pattern during at least two of the tasks. PEP and MSD demonstrated consistency, suggesting individual response stereotypy. Exhibiting a consistent pattern of decreased PEP and increased MSD was associated with less child- and parent-reported family conflict. These results are discussed in the context of vagal regulation of environmental demands.

Does locomotor response to novelty in rats predict susceptibility to develop sensitization to cocaine and PHNO?

It has been suggested that the locomotor response of rats to novelty is positively correlated with motor stimulant effects of acute injections with psychomotor stimulants, and liability to self-administer these drugs. In addition, response to novelty appears to be inversely correlated with an individual's susceptibility to develop behavioural sensitization (an increase in the behavioural response to a given dose of stimulant after repeated treatments). To test some of these putative relationships, 96 rats were allocated to one of two subgroups based on a median split of locomotor responses to novelty. Animals then received 10 successive injections of either vehicle, cocaine (10 mg/kg), or the direct D2 agonist, (+)-4-propyl-9-hydroxynaphthoxazine (PHNO: 15 microg/kg), and locomotor activity was monitored. Conditioning tests and additional sensitization and cross-sensitization tests were conducted. Results showed that locomotor responses to novelty are not significantly correlated with locomotor effects of either acute injection with cocaine or PHNO, or rate of development of behavioural sensitization to these drugs. However, locomotor responses to novelty did predict level of locomotor and stereotypy responses to cocaine, and to a lessor extent to PHNO. Cocaine-treated, but not PHNO-treated, rats exhibited drug-conditioned-like effects. Cross-sensitization between cocaine and PHNO was not observed, indicating independent mechanisms for sensitization. It is concluded that the locomotor response to novelty can predict level of locomotion and stereotypy produced by cocaine and PHNO, but does not predict the degree or rate of behavioural sensitization to either of these drugs.

Individual differences of the BOLD response stereotypy during activation paradigms

Individual differences of the BOLD response stereotypy during activation paradigms