Effects of amphetamine, morphine and dizocilpine (MK-801) on spontaneous alternation in the 8-arm radial maze

The induction of psychomotor activation, behavioural sensitization and of perseverative behaviours, resulting in reduced behavioural variability, have been proposed to be common properties of drugs of abuse. The present investigation tested whether these drug effects could be measured using spontaneous alternation in an 8-arm radial maze. Behavioural effects of repeated treatment with amphetamine (2 and 4 mg/kg, i.p.), morphine (1.25 and 10 mg/kg, i.p.) and the non-competitive NMDA receptor antagonist, MK-801 (0.1 and 0.2 mg/kg, i.p.), on spontaneous alternation were evaluated in this paradigm. All drugs induced psychomotor activation. Sensitized as well as reduced locomotor activity could be observed after repeated treatment depending on drug and dose. Analysis of the sequences of arm entries revealed that all drugs induced perseverative locomotor patterns, but the pattern induced by amphetamine and morphine differed qualitatively from the pattern induced by MK-801.     

Generalized and signal-specific long-term nociceptive sensitization in the snail Helix lucorum

Neurophysiological and behavioural correlates of the long-term sensitization were investigated in Helix lucorum small. Application of 10% quinine solution on the snail's head initiated a long-term (for more than 24 hours) facilitation of defensive reactions. The behavioural effects correlated with the changes in evoked and spontaneous activity of L-PP11 neurons, i.e., facilitation of synaptic components in responses to testing stimulation, increase in membrane excitability and depolarization. Efficacy of sensitization depended on the duration of the experimental procedure. After daily training site-specific and modality-specific effects dominated (i.e., more expressed facilitation of responses to testing stimulation of the sensitized body site than that of the other sites or to testing stimulation of the same modality as sensitizing stimulation). After 3 days of training the effects of general sensitization were predominantly observed, i.e., facilitation of neuronal responses to stimulation of different modalities and body sites, depolarization of the membrane and increase in its excitability.     

The role of inducible nitric oxide synthase in cardiac allograft rejection

Rats were exposed to either a footshock stimulus (FS) or emotional stimulus (ES, forced perception of another rat receiving footshocks) during a daily 10-min session for 5 consecutive days. The consequences of FS and ES on their behavioural responsiveness were assessed at different post-stress intervals using a small open-field. FS induced a decrease in ambulation, rearing and sniffing and an increased immobility in the small open field. These effects were present in rats tested immediately after the last session and remained present for at least 15 days. In contrast, ES induced a transient decrease in ambulation and rearing immediately after the last session, but in the period from half an hour until at least 15 days after the stimulus experience, an increase in ambulation, rearing and sniffing was observed. Exposure to one footshock per session for 5 consecutive days or to 10 footshocks in a single session also resulted in a long-lasting reduction in ambulation and sniffing and an increase in immobility. The former regime did not influence the behavioural response of ES rats, but the latter resulted in an increase in ambulation, rearing and sniffing in ES rats. Naloxone (1 mg/kg s.c.) pretreatment antagonized the increased behavioural activity of the ES rats whereas the activity of control and FS animals was not affected, suggesting an involvement of endogenous opioid systems in the behavioural responses observed in ES rats. It is suggested that the behavioural responses of the ES and FS animals are regulated by different mechanisms.     

Review of Weight Control: The Behavioural Strategies.

Reviews the book, Weight Control: The Behavioural Strategies by Michael D. LeBow (1981). This book does a more than adequate job in examining behavioural methods currently used in treatment of obesity. The influence of behaviour therapy on weight control is evaluated with realistic appraisals of its values and limitations. As an introduction for the novice therapist this book will be extremely valuable. Even the appendices of weight charts, skin fold measurement procedures, food calories and calorie expenditures may be used by the practitioner. The greatest limitation of the methodology presented and thus of the book itself, however, is the failure to recognize serious problems in behavioural technology (e.g., there is great variability in patients' responses to a behavioural program). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Does dizocilpine (MK-801) inhibit the development of morphine-induced behavioural sensitization in rats?

Intermittent morphine pretreatment (10 mg/kg/day for 14 days) induced long-lasting (one month post-treatment) sensitization to the locomotor effects of morphine and amphetamine in rats. Co-administration of the non-competitive NMDA-receptor antagonist dizocilpine (MK-801) (0.1 mg/kg) with morphine did not prevent the development of long-term behavioural sensitization. However, this dose of MK-801 did cause long-term sensitization to its own locomotor effects. Co-administration of 0.25 mg/kg MK-801 with morphine caused death in 60% of the animals. In the animals that survived MK-801 plus morphine pretreatment, neither short-term (3 days) nor long-term morphine-induced sensitization was observed. MK-801 alone (0.25 mg/kg/day for 14 days) induced short-term cross-sensitization to morphine. Thus, the development of long-term morphine-induced locomotor sensitization could only be prevented by a dose of MK-801 that yields a lethal combination with morphine. In addition, MK-801 induced sensitization to its own locomotor effects and cross-sensitization to morphine. These findings seriously question whether MK-801 can be used to study the development of morphine-induced behavioural sensitization.     

Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization

The present study was designed to evaluate the relationship between reinstatement of drug-seeking behaviour following long-term extinction of intravenous (i.v.) drug self-administration (an animal model for craving) and long-term behavioural sensitization. Rats were allowed to self-administer heroin (50 microg/kg per inj., 14 daily sessions), cocaine (500 microg/kg per inj., 10 daily sessions) or saline. Following a 3-week extinction period, reinstatement tests were performed to evaluate priming effects of amphetamine, cocaine and heroin on nonreinforced drug-seeking behaviour. In addition, the occurrence of long-term behavioural sensitization in rats with a history of heroin or cocaine self-administration was determined. Heroin-seeking behaviour was reinstated by heroin (0.25 mg/kg), amphetamine (1.0 mg/kg) and cocaine (10 mg/kg). In addition, animals with a history of heroin self-administration displayed locomotor sensitization to both heroin and amphetamine. Cocaine-seeking behaviour was reinstated by cocaine and amphetamine, but not by heroin. Interestingly, locomotor sensitization to amphetamine, but not heroin, was observed in animals with a history of cocaine self-administration. In other words, the induction of drug-seeking behaviour following a prolonged drug-free period was found to be associated with the expression of long-term behavioural sensitization. These data provide experimental evidence for a role of behavioural sensitization in the incentive motivation underlying drug-seeking behaviour. If drug hyperresponsiveness would indeed be a crucial factor in drug-induced craving in human addicts, pharmacological readjustment of the neuroadaptations underlying drug sensitization may prevent relapse to drug use long after detoxification.     

Modulation of morphine-induced sensitization by endogenous kappa opioid systems in the rat

Sensitization to both the motor stimulant and mesolimbic dopamine-releasing effects of morphine were studied in animals chronically treated with morphine and those that had received the kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI) prior to the commencement of morphine treatment. Rats were pretreated with either nor-BNI (30 micrograms; i.c.v.) or its vehicle and then received injections of morphine for 10 days. Locomotor activity and microdialysis studies were then conducted 3 and 30 days after termination of the chronic morphine treatment. In chronic morphine-treated rats, sensitization developed to both the motor stimulatory effects of morphine and the mesolimbic dopamine-releasing effects of this drug. Sensitization was observed 3 and 30 days after termination of morphine treatment. In animals pretreated with nor-BNI, sensitization to both the motoric and dopamine-releasing effects of morphine was significantly greater than that of chronic morphine-treated rats. These results suggest that endogenous kappa opioid systems play an important role in morphine-induced sensitization and that manipulations of these systems can markedly influence both its behavioral and neurochemical expression.     

The effect of nigral implantation on sensitization to dopamine agonists in 6-hydroxydopamine-lesioned rats

The implantation of fetal nigral tissue into the striatum of patients with Parkinson's disease is a promising approach to treatment which may produce clinical benefit partly by influencing drug responsiveness. The purpose of the present study was to determine the pharmacological mechanisms which drug response changes by measuring to what extent sensitization produced by repeated apomorphine treatment was attenuated by tissue implantation in rats with nigrostriatal lesions. Prior to implantation of nigral cell suspensions, the daily administration of apomorphine to rats with unilateral 6-hydroxydopamine lesions produced a progressive increase in the magnitude and duration of rotational behaviour. After implantation, apomorphine-induced rotational effects were reduced to levels observed upon the initial exposure to drug and did not increase following repeated treatment. Attenuated responses to selective D1 and D2 agonists were also observed after implantation. In vehicle-implanted rats, the initial response to apomorphine was attenuated but then increased following repeated apomorphine administration. No attenuation in responses to selective D1 and D2 agonists was observed in this group. Cell suspensions prepared from fresh and cyropreserved tissue produced similar behavioural effects, even though the volume of transplanted striatum exhibiting tyrosine hydroxylase activity was greater with fresh tissue. The duration of rotational behaviour induced by apomorphine was not affected by cell implantation. These findings suggest that the expression of sensitization in an animal model of parkinsonism may disappear after a period without drug treatment. Implantation of nigral tissue may produce beneficial results in parkinsonism by limiting the development of dopamine agonist-induced sensitization.     

Release of renin from glomeruli isolated from rat kidney

Cardiovascular and behavioural responses elicited by novel, noxious or aversive stimuli have been studied in dogs and cats. Hindlimb blood flow, heart rate and arterial blood pressure increased in dogs when an orienting response was elicited by a novel stimulus (a sound). Similar cardiovascular responses occurred in dogs to mild noxious stimulus and in cats displaying a threatening posture when confronted by a dog. The cardiovascular components of the orienting response to a sound habituated with repetition of the sound. In two dogs however sensitization (increase) of the response occurred with reped by repetition of the confrontations: the vasodilation in the muscles waned and eventually was replaced by vasoconstriction while the cardiac acceleration and pressor response persisted. The threatening response was the most persistent. The modification of the behavioural and cardiovascular aspect of the response was not developing in parallel. The cardiovascular pattern was altered before any apparent changes of the behavioural pattern occurred. The cardiovascular responses of the noxious stimulus in dogs and cardiovascular components of the defence reaction in cats were readily conditioned to a sound. The possible role of the modification of the cardiovascular pattern in defence reactions in pathogenesis of hypertension is discussed.     

Endocrine and behavioural responses to noise stress: comparison of virgin and lactating female rats during non-disrupted maternal activity

The behavioural and endocrine responses to a 10 min white noise stress have been characterized in female virgin and undisturbed lactating Sprague-Dawley rats. Animals were continuously video-taped and frequent blood samples were collected using an automated sampling system. Noise stress caused hypothalamo-pituitary-adrenal (HPA) activation, as indicated by a rapid increase in plasma corticosterone and ACTH in the virgins: corticosterone concentrations peaked 20 min after initiation of the stress before declining rapidly back to basal concentrations. In contrast, noise stress had no significant effect on either plasma corticosterone or ACTH concentrations in the lactating animals. However, 72 h after weaning the corticosterone response of the ex-lactating rats was of comparable magnitude, but longer duration to that seen in the virgins. Plasma prolactin concentrations were significantly higher in the lactating animals and declined in response to the noise whereas, a transient but reproducible increase was seen in the virgin group. In situ hybridization revealed a significantly lower basal expression of CRF mRNA in the paraventricular nucleus of lactating rats as compared to the virgins, but noise stress had no further effect. Virgin animals showed behavioural responses to the stress, including an increase in the total activity, exploratory behaviours (rearing) and displacement behaviours (grooming). Lactating animals also showed behavioural responses to the noise, but their activities were principally directed towards the pups. These data show that although lactating rats showed normal behavioural reactivity to a psychological stress they showed no statistically significant activation of the HPA axis, suggesting a dissociation of behavioural and neuroendocrine responses to this mild stress.     

Systemic administration of atipamezole, a selective antagonist of alpha-2 adrenoceptors, facilitates behavioural activity but does not influence short-term or long-term memory in trimethyltin-intoxicated and control rats

The present study used trimethyltin (TMT)-intoxicated rats as a model for the behavioural syndrome seen after neuronal damage to the limbic system. Behavioural assessments indicated increased locomotor activity and reduced number of groomings in an open-arena task in TMT-intoxicated (6.6 mg/kg as a free base) rats, as has been found previously. A novel finding was the severe deficit in swimming to a visible platform in the water maze task, with reduced swimming speed at the beginning of the training period. During the reacquisition phase of a radial arm maze task, TMT-intoxicated rats made more short-term and long-term memory errors, and their behavioural activity was increased in comparison with controls. The administration of atipamezole (300 micrograms/kg), a selective antagonist of alpha 2-adrenoceptors, enhanced locomotor activity compared to saline-treated rats, but these effects did not differ between the TMT group and their controls. Atipamezole did not enhance short-term or long-term memory in either TMT or control groups. Taken together, the present data indicate that TMT intoxication is a model for global dementia rather than for a specific loss of relational memory. Previous studies on the neurochemical effects of TMT and the alleviation or prevention of neurotoxicity of TMT are reviewed.     

A phase II study of i.v. methylprednisolone in secondary-progressive multiple sclerosis

We have used rats with streptozotocin-induced diabetes to investigate the effects of hyperglycaemia-mediated impaired nucleoside uptake on the actions of endogenous adenosine in hippocampal slices. In control tissue under conditions of anoxia and aglycaemia the rise in the extracellular adenosine concentration resulted in complete inhibition of synaptic activity in about 2 min. In slices from previously hyperglycaemic rats the inhibition of synaptically mediated responses occurred significantly faster, although this change could be prevented by insulin treatment. Application of the selective adenosine A1 receptor antagonist [8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] prevented the anoxia/aglycaemia-mediated inhibition and, furthermore, abolished the differences in the electrophysiological responses between control and diabetic tissue. The effects of impaired nucleoside uptake could be mimicked in control slices by applying the nucleoside uptake blocker hydroxynitrobenzylthioinosine (HNBTI). This had the effect of speeding up the rate of anoxia/aglycaemia-induced synaptic inhibition in control tissue to that seen in diabetic tissue. However, such treatment had no effect on the responses in diabetic tissue as expected if the HNBTI-sensitive uptake process was already inhibited by the chronic hyperglycaemia. The impairment of nucleoside uptake by chronic hyperglycaemia results in the potentiation of the modulatory actions of endogenous adenosine in the central nervous system. Such an alteration in adenosine function may be important in explaining behavioural and pathological changes associated with diabetes mellitus.     

La recherche en psychologie pour une meilleure politique de l'environnement.

As Environment Minister, I have had the unique opportunity to travel across the country, meeting individual Canadians who are working for the environment in their own communities. As a government, it is our responsibility to ensure that the policies and programs are in place to support their work. It is also our responsibility to try to spur others on to similar action, and to build public support for a sustainable environment. We cannot do this if we do not adequately understand the links between attitude, behaviour, and preservation of our environment. I commend the Canadian Journal of Behavioural Science for focussing on the behavioural origins of environmental solutions. I hope that the issues raised in the articles contained herein spur many of you to consider how research can help us answer some of the questions I have raised. The participation of the behavioural sciences is essential, not only to the success of environment protection, but to its very feasibility. Well-conceived research is essential in order to engage and retain public support and thus devise responses that are both environmentally sound and economically possible. Here is a challenge worthy of your expertise. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychology research for environmental policy.

As Environment Minister, I have had the unique opportunity to travel across the country, meeting individual Canadians who are working for the environment in their own communities. As a government, it is our responsibility to ensure that the policies and programs are in place to support their work. It is also our responsibility to try to spur others on to similar action, and to build public support for a sustainable environment. We cannot do this if we do not adequately understand the links between attitude, behaviour, and preservation of our environment. I commend the Canadian Journal of Behavioural Science for focussing on the behavioural origins of environmental solutions. I hope that the issues raised in the articles contained herein spur many of you to consider how research can help us answer some of the questions I have raised. The participation of the behavioural sciences is essential, not only to the success of environment protection, but to its very feasibility. Well-conceived research is essential in order to engage and retain public support and thus devise responses that are both environmentally sound and economically possible. Here is a challenge worthy of your expertise. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tumour necrosis factor-alpha and interleukin-2 differentially affect hippocampal serotonergic neurotransmission, behavioural activity, body temperature and hypothalamic-pituitary-adrenocortical axis activity in the rat

Intraperitoneal endotoxin injection and central administration of interleukin (IL)-1beta profoundly activate hippocampal serotonergic neurotransmission. This study was designed to investigate, using in vivo microdialysis, the effects of another endotoxin-induced proinflammatory cytokine, tumour necrosis factor-alpha, and the effects of the non-inflammatory cytokine, IL-2, on hippocampal extracellular levels of serotonin. To compare the effects of these cytokines on neurotransmission with the effects on physiological parameters and behaviour, hypothalamic-pituitary-adrenocortical (HPA) axis activity, body temperature and behavioural activity were monitored as well. Time-dependent changes in serotonergic neurotransmission and HPA axis activity were determined by measuring serotonin, its metabolite 5-hydroxyindoleacetic acid and free corticosterone in dialysates. Total behavioural activity was scored by assessing the time during which rats were active. Core body temperature was measured by biotelemetry. Intracerebroventricular injection of 50 or 100 ng recombinant murine tumour necrosis factor-alpha exerted no effect on hippocampal serotonergic neurotransmission, and induced no signs of sickness behaviour. However, these doses produced a dose-dependent increase in body temperature and free corticosterone levels. In contrast, intracerebroventricular administration of 500 ng, but not of 50 ng, recombinant human IL-2 produced a marked increase in hippocampal extracellular concentrations of serotonin and 5-hydroxyindoleacetic acid, accompanied by a pronounced behavioural inhibition and other signs of sickness. Moreover, both doses of IL-2 caused a dose-dependent increase in body temperature and free corticosterone levels. Interestingly, intracerebroventricular pretreatment with the IL-1 receptor antagonist showed that the effects of IL-2 on hippocampal serotonin were completely dependent on endogenous brain IL-1. However, IL-1 seemed to play only a minor role in the IL-2-induced increase in free corticosterone. Taken together, the results show that cytokines produce partially overlapping brain-mediated responses, but are selectively effective in stimulating hippocampal serotonergic neurotransmission and inducing sickness behaviour. Moreover, we postulate that activation of hippocampal serotonin release is instrumental in the full development of behavioural inhibition.     

Psychosocial adjustment of children treated for anorectal anomalies

The psychosocial adjustment of 160 children with anorectal malformations was assessed at 6 to 17 years of age in relation to levels of continence (Kelly score). Five measures of emotional and behavioural adjustment were used to assess a number of domains of child/adolescent functioning and to include measures from multiple perspectives. The psychiatric assessment of the child identified a disorder in 29% of the group overall. Based on parental assessments, behavioural maladjustment was shown in 27% of the children, and on the basis of a self-report questionnaire 24% of the children were depressed. Behavioural adjustment as rated by teachers was similar to the norms. The level of continence achieved (total Kelly score) did not appear to influence psychological adjustment, with the exception of the incontinent young girls (6 to 11 years) who were shown to be less well adjusted than the continent young girls. Differences between children showing positive versus negative adjustment were dependent on the perspective of the respondent and were also related to the child's age and gender, age of achieving continence, frequency of accidents, and parental factors.     

Behavioral science at work for Canada: National Research Council laboratories.

The National Research Council is Canada's principal research and development agency. Its 20 institutes are structured to address interdisciplinary problems for industrial sectors, and to provide the necessary scientific infrastructure, such as the national science library. Behavioural scientists are active in five institutes: Biological Sciences, Biodiagnostics, Aerospace, Information Technology, and Construction. Research topics include basic cellular neuroscience, brain function, human factors in the cockpit, human-computer interaction, emergency evacuation, and indoor environment effects on occupants. Working in collaboration with NRC colleagues and with researchers from universities and industry, NRC behavioural scientists develop knowledge, designs, and applications that put technology to work for people, designed with people in mind. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The dominance of behavioural activation over behavioural inhibition in conduct disordered boys with or without attention deficit hyperactivity disorder

On the basis of Gray's theory, Quay suggested that conduct disorder (CD) is associated with a Behavioural Activation System (BAS) that dominates over the Behavioural Inhibition System (BIS), whereas attention deficit hyperactivity disorder (ADHD) is characterised by an underactive BIS. Two studies were conducted to test the hypothesis that the dominance of the BAS over the BIS is more pronounced in CD comorbid with ADHD (CD/ADHD) than in CD alone. First of all, a response perseveration task was used, i.e. the door-opening task (Daugherty & Quay, 1991). In this game, the subject chooses either to open the next door or to stop playing; there is a steadily increasing ratio of punished responses to rewarded responses and a large number of doors opened is indicative of response perseveration. As expected, a steady increase in the number of doors opened was found across normal control (NC) boys, CD boys, and CD/ADHD boys (NC < CD < CD/ADHD). Second, the dominance of the BAS over the BIS was examined by observing the social behaviour of the child in interaction with a research assistant who alternately activated the BAS and the BIS while a game was played. The behaviour of the children was analysed according to ethological methods. Group differences in the frequencies of three out of five behavioural categories were in line with the results of the door-opening task (NC < CD < CD/ADHD).     

Agonist-specific coupling of a cloned Drosophila melanogaster D1-like dopamine receptor to multiple second messenger pathways by synthetic agonists

The mechanism of coupling of a cloned Drosophila D1-like dopamine receptor, DopR99B, to multiple second messenger systems when expressed in Xenopus oocytes is described. The receptor is coupled directly to the generation of a rapid, transient intracellular Ca2+ signal, monitored as changes in inward current mediated by the oocyte endogenous Ca2+-activated chloride channel, by a pertussis toxin-insensitive G-protein-coupled pathway. The more prolonged receptor-mediated changes in adenylyl cyclase activity are generated by an independent G-protein-coupled pathway that is pertussis toxin-sensitive but calcium-independent, and Gbetagamma-subunits appear to be involved in the transduction of this response. This is the first evidence for the direct coupling of a cloned D1-like dopamine receptor both to the activation of adenylyl cyclase and to the initiation of an intracellular Ca2+ signal. The pharmacological profile of both second messenger effects is identical for a range of naturally occurring catecholamine ligands (dopamine > norepinephrine > epinephrine) and for the blockade of dopamine responses by a range of synthetic antagonists. However, the pharmacological profiles of the two second messenger responses differ for a range of synthetic agonists. Thus, the receptor exhibits agonist-specific coupling to second messenger systems for synthetic agonists. This feature could provide a useful tool in the genetic analysis of the roles of the multiple second messenger pathways activated by this receptor, given the likely involvement of dopamine in the processes of learning and memory in the insect nervous system.     

Social relationships and the management of stress

Two different types of social relationships exist in mammalian social systems: dominance relationships and social bondings. This article shows that both are crucial for the management of stress. The following general conclusions are derived: (1) In stable social systems, established dominance relationships result in predictable behaviour. As a consequence, low positions in the hierarchy do not necessarily lead to enhanced endocrine stress responses. Under conditions of instability, however, distinct increases in the activities of the pituitary-adrenocortical- and the sympathetic-adrenomedullary systems are found; (2) The ability to establish and to respect dominance relationships is a prerequisite to build up stable social systems. Whether this ability is realized, however, depends on social experiences made during behavioural development. The time around puberty seems to be essential for the acquisition of those social skills needed to adapt to unfamiliar conspecifics in a non-stressful and non-aggressive way; (3) Stress responses can be ameliorated by the presence of members of the same species. This phenomenon is called social support. In general, social support cannot be provided by any conspecific, but the ability to give social support is restricted to bonding partners. In most mammalian species mothers are important bonding partners for their infants. In some species bondings also occur between adult individuals; and (4) On a physiological level the bonding partner reduces the activities of the pituitary-adrenocortical- and the sympathetic-adrenomedullary systems. On a psychological level he/she can be regarded as a 'security-giving and arousal-reducing structure'. This is true irrespective of whether the bonding partner is the mother, in the case of an infant, or a male or a female in the case of an adult individual.