Amphetamine increases intertrial but not conditional instrumental responding in the cortico-basomedial amygdalar dogs

The effect of partial cortico-basomedial amygdaloid lesions on dogs' social behavior was investigated. The lesions did not affect the conditional instrumental responding (CRs) reinforced by petting or the dogs' need for petting (US). The lesions increased the number of intertrial responses (ITRs) in all dogs. Subsequently the effect of low amphetamine doses (0.5 mg/l kg) administered intramuscularly to the amygdalar animals on the same behavioral parameters of the social behavior was examined. Amphetamine did not affect CRs but dramatically increased the ITRs and dogs' need for petting. These findings suggest that the cortico-basomedial amygdaloid region may be involved in the cortical inhibitory mechanisms that are indispensable for promoting behavioral acts according to their usefulness and the situational context.     

Psychopharmacologic facilitation of psychosocial therapy of violence and hyperkinesis

Experiments on naturally occurring hyperkinetic and violent dogs and cats demonstrated the usefulness of low dosages of amphetamine (0,2-1,0 mg/kg per os) in inhibiting these nonadaptive forms of behavior, permitting the development of discriminated Pavlovian and operant conditional responses. When amphetamine therapy was combined systematically with conditioning experiments and psychosocial therapy, for long enough periods of time (many weeks), the beneficial effects of this drug persisted in the nodrug state, i.e. the learning was not state-dependent. Amphetamine also ameliorated significantly conditional emotional visceral responses in dogs with low adaptation to psychologically stressful situations. The same low dosage of amphetamine which improved the behavior and learning of hyperkinetic and violent dogs disrupted the behavior and produced disorientation in normal dogs with previously stable conditional responses.     

Early Pavlovian studies on the effects of starvation. A contribution to the history of neurodietetics

This communication is based on the pioneering studies performed by I. P. Pavlov's associates, Yu. P. Frolov (in 1918) and I. S. Rozental' (in 1918/1919) at the Institute of Experimental Medicine, in Petrograd. The changes in the "independent variable"--the dogs' diet--were not planned but were the consequences of severe shortages of food for man and beast. The principal generalization concerns the order in which different forms of "complex nervous activity" were impaired: the order is opposite to the order in which they emerge in the process of ontogenesis. First to suffer was "internal inhibition," as documented by the failure of stimulus differentiation. This was followed by the decrease in the magnitude of well-established conditional responses (CRs). As a result of a more severe impairment of the excitatory processes, it became difficult or impossible to establish new CRs. In time, previously established CRs to artificial stimuli, visual and acoustic, disappeared totally. The CRs to natural conditional stimuli (CSs) were maintained fairly well but, eventually, they too decreased markedly. In the terminal phase of starvation, the unconditional salivary reflexes continued to function, although their magnitude was depressed.     

Repeated treatment with the kappa opioid receptor agonist U69593 reverses enhanced K+ induced dopamine release in the nucleus accumbens, but not the expression of locomotor sensitization in amphetamine-sensitized rats

The effects after the acute activation of the kappa opioid receptor (KOR) can be distinguished from the effect after repeated administration of KOR agonist. Here, we report the effect of repeated administration of U69593 during abstinence after amphetamine-induced locomotor sensitization. Rats were injected once daily with amphetamine for five consecutive days. From day 6 to 9, rats that developed locomotor sensitization, received once daily injection of U69593 or vehicle. On day 10, all rats were injected with a challenging dose of amphetamine and locomotor activity was measured to assess the expression of sensitization. Microdialysis studies were carried out to assess dopamine extracellular levels in NAc. Rats that develop and express horizontal locomotor sensitization to amphetamine show increased dopamine release in the NAc induced by high K(+). The repeated treatment with U69593 reverses the sensitized depolarization-stimulated dopamine release in the NAc, but not the expression of locomotor sensitization induced by amphetamine. Thus, repeated activation of KORs during early amphetamine withdrawal dissociates the behavioral responses and the neurochemical responses that accompany the expression of sensitization to amphetamine.     

Retreat space and human visitor density moderate undesirable behavior in petting zoo animals

This study focused on the relationship between nonhuman animal behavior and environment-specifically, between the undesirable behavior exhibited by domestic petting zoo animals in the presence of humans and the spatial design of the petting zoo environment. A spatial feature of a petting zoo referred to as a retreat space was manipulated so that it affected the animals' opportunity for individual control over interaction with humans. Three conditions were tested: no retreat space, semi-retreat space, and a full-retreat space. The subjects of this study were 5 African pygmy goats (Capra hircus) and 2 Romanov sheep (Ovis aries). Investigators used a focal sampling technique to analyze approximately 27 hr of behavioral data collected. The data were analyzed using multiple linear regression methods. The findings suggest that the full-retreat design beneficially moderated both sheep and goat behavior: Undesirable behaviors were lowest in the full-retreat condition. This study provides information that may improve human-animal interactions in a petting zoo setting and may increase animal well-being through exhibit design and management techniques.     

Responses of cats to petting by humans

Abstract

There is evidence that different gland areas in animals of the cat family have different functions. This study showed that nine cats gave more positive and fewer negative responses to petting by their owners in the temporal region (between the eyes and ears), the reverse to petting in the caudal region (around the tail), with the perioral (chin and lips) and non-gland areas intermediate. This suggests that cats prefer being petted in certain body areas.     

Centrally administered vasopressin cross-sensitizes rats to amphetamine and drinking hypertonic NaCl

Prior sodium restriction cross-sensitizes rats to the psychomotor effects of amphetamines and vice versa. Repeated central injections of vasopressin (VP) induce a psychomotor sensitization similar to amphetamine sensitization and repeated sodium deficiency. Thus brain VP signaling may be a common mechanism involved in mediating these two motivational systems. In experiment 1, we tested the hypothesis that rats previously sensitized to central VP would show enhanced psychomotor responses to amphetamine. Rats were administered saline, VP (50 ng), or amphetamine (1 mg/kg or 3 mg/kg) on days 1 and 2, and given saline or amphetamine on day 3. Amphetamine produced psychomotor arousal in all groups. However, amphetamine on day 3 elicited a significantly greater psychomotor response in rats that had prior injections of amphetamine or VP than in rats previously treated with saline. In experiment 2, the hypothesis that prior experience with central VP would cross-sensitize rats to drinking hypertonic sodium (NaCl) solutions was tested. Rats were administered VP (50 ng) or saline for 3 days. On the fourth day, nondeprived rats were given access to 0.3 M NaCl and water for 1 h. Control and saline-treated rats only drank 1 ml of 0.3 M NaCl, but rats previously exposed to central VP drank significantly more hypertonic saline (4 ml). These results show that prior experience with central VP cross-sensitizes rats to the psychomotor stimulant effects of amphetamine and the ingestion of concentrated NaCl solutions. This pattern of cross-sensitization links central VP signaling, amphetamine, and sodium deficiency, and therefore it may play a role in the cross-sensitization between sodium appetite and amphetamines.     

Retreat Space and Human Visitor Density Moderate Undesirable Behavior in Petting Zoo Animals

This study focused on the relationship between nonhuman animal behavior and environment-specifically, between the undesirable behavior exhibited by domestic petting zoo animals in the presence of humans and the spatial design of the petting zoo environment. A spatial feature of a petting zoo referred to as a retreat space was manipulated so that it affected the animals' opportunity for individual control over interaction with humans. Three conditions were tested: no retreat space, semi-retreat space, and a full-retreat space. The subjects of this study were 5 African pygmy goats (Capra hircus) and 2 Romanov sheep (Ovis aries). Investigators used a focal sampling technique to analyze approximately 27 hr of behavioral data collected. The data were analyzed using multiple linear regression methods. The findings suggest that the full-retreat design beneficially moderated both sheep and goat behavior: Undesirable behaviors were lowest in the full-retreat condition. This study provides information that may improve human-animal interactions in a petting zoo setting and may increase animal well-being through exhibit design and management techniques.     

Comparative study of cathinone and amphetamine on brown adipose thermogenesis

The effect of cathinone and amphetamine on brown adipose tissue thermogenesis and its modification with propranolol and timolol has been studied in rats. Both cathinone and amphetamine produced significant dose dependent increases in intracapsular brown adipose tissue (IBAT) and rectal temperatures. Amphetamine was found to be three times more potent as compared to cathinone, on a dose basis. Pretreatment of animals with propranolol and timolol individually inhibited cathinone and amphetamine induced hyperthermia. These findings suggest the involvement of beta adrenergic receptors in cathinone and amphetamine induced thermogenesis.     

Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class

The demonstrated ability of amphetamine to functionally activate the rat trace amine associated receptor 1 (rTAAR1) and the subsequent reports of amphetamine activation of TAAR1 in rhesus monkey mouse, human, and human-rat chimeric TAAR1-expressing cell lines has led to speculation as to the role of this receptor in the central nervous system (CNS) responses associated with amphetamine and its analogs. The agonist potencies of ten pairs of enantiomeric amphetamines, including several with known CNS activity, at primate TAAR1 stably expressed in RD-HGA16 cells, robustly indicate the S-configuration to be associated with higher potency. Moreover, the rank order of potency to activate TAAR1 parallels the stimulant action reported by humans for the specific amphetamines. Taken together, these data suggest that TAAR1 is a stereoselective binding site for amphetamine and that activation of TAAR1 is involved in the modulation of the stimulant properties of amphetamine and its congeners. In addition, the observed parallel between hTAAR1 and rhTAAR1 responses supports the rhesus monkey as a highly translational model for developing novel TAAR1-directed compounds as therapeutics for amphetamine-related addictions.     

Salviae miltiorrhizae Radix Inhibits Superoxide Generation by Activated Rat Microglias and Mimics the Action of Amphetamine on in vitro Rat Striatal Dopamine Release

Salviae miltiorrhizae Radix (SMR), an eminent herb in the treatment of cardiovascular disorder (called blood stasis in traditional Chinese medicine), is widely used in China, Japan, Taiwan and Korea. SMR is also herbal medicines used in the treatment of drug addiction without scientific support for their mechanism of action. We evaluated the effect of SMR on superoxide production by rat microglias using a 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin-3-one-dependent chemiluminescence assay. SMR dose-dependently inhibited superoxide production by microglias stimulated with phorbol myristate acetate or opsonized zymosan, while it had no effect on superoxide production by a hypoxanthinexanthine oxidase system. These results indicate that SMR does not have a scavenging effect, but has an inhibitory effect on superoxide generation by microglias. Although SMR is commonly used for treating chronic cerebral infarction, it may also have a protective effect on progression of Parkinson's disease or Alzheimer's disease. On the other hand, the present study investigated the effect of the medicinal plant on dopaminergic neurotransmission in comparison with amphetamine. The effect of crude water extracts (0.1 g/ml) of SMR on K+ (20 mM)-stimulated dopamine release from rat striatal slices was compared with amphetamine (10(-4) M) using high-performance liquid chromatography with electrochemical detection to measure endogenous dopamine. Amphetamine and SMR significantly increased K+-stimulated dopamine release (P<0.001) from rat striatal slices when compared with K+-stimulated alone. SMR potentiated the effect of amphetamine on K+-stimulated dopamine release (P<0.001) when compared with amphetamine alone. The results indicate that SMR may stimulate dopamine release in the same manner as amphetamine. It remains to be determined whether the effect of this extract on dopamine function is important in its therapeutic use in the treatment of drug addiction.     

Dopamine receptor antagonists reverse amphetamine-induced behavioral alteration on a differential reinforcement for low-rate (DRL) operant task in the rat

Previous studies have shown that amphetamine significantly alters operant responding on the behavior maintained on a schedule of differential reinforcement of low-rate (DRL). As such, behavioral deficiency of DRL responding has been observed by the drug-induced increase of non-reinforced responses and a leftward shift of inter-response time (IRT) curve on DRL responding in the rat. However, the neurochemical basis for amphetamine-induced DRL behavioral alternations remain to be elucidated. The present study was then designed to examine whether the effects of amphetamine were dependent on dopamine-subtyped receptors, this was carried out by the co-administration of the selective D1 and D2 receptor antagonists, SCH23390 and raclopride respectively. Rats were first trained to perform on DRL 10-sec task and then divided into four groups, which received separate types of double injections before the behavioral session. The four groups were the saline control group, the amphetamine alone group, the dopamine antagonist alone group, and the combination of [corrected] amphetamine and dopamine antagonist group. The saline control group performed DRL responding in an efficient manner with a major index for the peak time of the IRT curve, which was fairly localized within the 10-sec bin throughout the test phase. The subjects injected with amphetamine (1 mg/kg) significantly shortened IRT that led to a leftward shift of IRT curve, which was further revealed by a decreased peak time without significant effectiveness on the peak rate and burst response. Even though the group given SCH23390 or raclopride alone showed profound disruption on DRL behavior by flattening the IRT curve, the co-administration of amphetamine with SCH23390 or raclopride reversed the aforementioned amphetamine-induced behavioral deficiency on DRL task. Together, these results suggest that the dopamine D1 and D2 receptors are involved and important to the temporal regulation of DRL response under psychostimulant drug treatment. Furthermore, this highlights the involvement of the brain dopamine systems in the temporal regulation of DRL behavior performance.     

Genetics of novelty seeking,amphetamine self‐administration and reinstatement using inbred rats

Previous research using outbred rats indicates that individual differences in activity in a novel environment predict sensitivity to the reinforcing effect of psychostimulant drugs. The current study examined if the link between responses related to novelty and amphetamine self‐administration is heritable. Twelve inbred rat strains were assessed for locomotor activity in a novel environment, preference for a novel environment, and intravenous amphetamine self‐administration (acquisition, extinction and amphetamine‐induced reinstatement). Strain differences were observed in activity in a novel environment, novelty preference and amphetamine self‐administration, indicating a genetic influence for each of these behaviors. While there was no relation between activity in an inescapable novel environment and amphetamine self‐administration, strain‐dependent differences in novelty preference were positively correlated with the amount of amphetamine self‐administered. There was also a positive correlation between the dose‐dependent rate of amphetamine self‐administration and magnitude of reinstatement. These results show that the activity in an inescapable novel environment and the preference for a novel environment are different genetically, and thus likely to reflect different behavioral constructs. Moreover, these results implicate a genetic influence on the relation between novelty seeking and stimulant self‐administration, as well as on the relation between stimulant reward and reinstatement.     

Acute amphetamine down-regulates RGS4 mRNA and protein expression in rat forebrain: distinct roles of D1 and D2 dopamine receptors

Administration of psychostimulants modulates mRNA of several regulators of guanine nucleotide-binding protein signaling (RGSs) proteins in the brain. In the present study, the regulation of amphetamine-induced decrease of RGS4 expression in the rat forebrain was evaluated. RGS4 mRNA was reduced by amphetamine in an inverse, dose-dependent manner. The lowest dose (2.5 mg/kg) decreased RGS4 mRNA in caudate putamen for up to 6 h after injection whereas the decrease in several frontal cortical areas was detected at 3 h only. Analysis of RGS4 immunoreactivity by western blotting revealed a decrease 3 h after amphetamine solely in the caudate putamen. Systemic administration of D(1) (SCH23390) or D(2) (eticlopride) receptor antagonists blocked amphetamine-induced locomotion but amphetamine augmented both the SCH23390-induced increase and the eticlopride-induced decrease in RGS4 mRNA in the caudate putamen. Further, the down-regulation of RGS4 immunoreactivity by eticlopride was robust whereas the effect of SCH23390 was blunted as compared with its effect on mRNA. These data suggest that, by decreasing RGS4 expression in the caudate putamen via D(1) receptors, acute amphetamine could disinhibit RGS4-sensitive guanine nucleotide-binding protein alpha-subunit i- and/or q-coupled signaling pathways and favor mechanisms that counterbalance D(1) receptor stimulation.     

Chronic pretreatment with methylphenidate induces cross-sensitization with amphetamine

Consequence of the long-term use of psychostimulants as treatment for attention deficit/hyperactivity disorder (ADHD) is unknown, particularly whether treatment with psychostimulants at an early age increases an individual's potential for cross-sensitization to other stimulants exposed at a later age. Cross-sensitization occurs when pretreatment with one stimulant leads to greater sensitivity to another stimulant. The aims of this study were to investigate whether chronic treatment with methylphenidate (MPD; Ritalin) in both juvenile and adult rats induced cross-sensitization to amphetamine at a later time and whether this cross-sensitization to amphetamine was age-dependent. Male Sprague-Dawley rats were randomly divided into four treatment groups: (1) group treated intraperitoneally (i.p.) with saline as juveniles and adults, (2) group treated with 0.6 mg/kg amphetamine, i.p., as juveniles and adults, (3) group treated with 2.5 mg/kg MPD, i.p., as juveniles and adults, and (4) group treated with saline, i.p., as juveniles and 2.5 mg/kg MPD, i.p., as adults. All of the animals received an amphetamine (0.6 mg/kg, i.p.) challenge on the last experimental day. We examined the effects of chronic MPD treatment in juvenile and adult rats on their locomotor response to an acute amphetamine exposure. Three different locomotor indices were studied using an automated activity monitoring system. Changes in the locomotor responses to amphetamine of these animals were compared to those of control rats that were pretreated with saline as juveniles and as adults. It was found that prior chronic treatment with MPD produced cross-sensitization to the locomotor response to amphetamine as observed in the horizontal activity and total distance traveled. It also appears that this cross-sensitization to amphetamine may not be dependent on the age of the subjects, i.e., whether subjects were juvenile or adult rats when they received drugs, but rather it depended on the behavioral index examined.     

Affiliative and disciplinary behavior of human handlers during play with their dog affects cortisol concentrations in opposite directions

It has been shown that cortisol concentrations change characteristically in the course of agonistic interactions; our aim was to find out how a playful situation may affect concentrations of this hormone in the saliva. We studied dogs' behavior and the changes of cortisol concentrations in a play situation, where the dogs played with their handler for 3 min with a tug toy. In this experiment working dogs were divided into two groups by the type of their work, namely police dogs and border guard dogs. We found that the cortisol concentrations of old police dogs significantly increased, while the adult border guard dogs' hormone levels decreased, which shows that playing with the handler has an effect on both groups, but interestingly this effect was opposite. Behavior analysis showed differences only in the behavior of the human handlers during the play sessions, while the behavior analysis did not reveal significant differences in the two groups of dogs, except that old border guard dogs generally needed more time to begin playing than old police dogs. During the play sessions police officers were mainly disciplining their dogs, while the border guards were truly playing with them (including affiliative and affectionate behavior). Our results are in accordance with those of recent studies, which show that behaviors associated with control, authority or aggression increase cortisol concentrations, while play and affiliative behavior decrease cortisol levels.     

Effects of Methylphenidate on Extracellular Dopamine, Serotonin, and Norepinephrine: Comparison with Amphetamine

Abstract: Methylphenidate promotes a dose-dependent behavioral profile that is very comparable to that of amphetamine. Amphetamine increases extracellular norepinephrine and serotonin, in addition to its effects on dopamine, and these latter effects may play a role in the behavioral effects of amphetamine-like stimulants. To examine further the relative roles of dopamine, norepinephrine, and serotonin in the behavioral response to amphetamine-like stimulants, we assessed extracellular dopamine and serotonin in caudate putamen and norepinephrine in hippocampus in response to various doses of methylphenidate (10, 20, and 30 mg/kg) that produce stereotyped behaviors, and compared the results with those of a dose of amphetamine (2.5 mg/kg) that produces a level of stereotypies comparable to the intermediate dose of methylphenidate. The methylphenidate-induced changes in dopamine and its metabolites were consistent with changes induced by other uptake blockers, and the magnitude of the dopamine response for a behaviorally comparable dose was considerably less than that with amphetamine. Likewise, the dose-dependent increase in norepinephrine in response to methylphenidate was also significantly less than that with amphetamine. However, in contrast to amphetamine, methylphenidate had no effect on extracellular serotonin. These results do not support the hypothesis that a stimulant-induced increase in serotonin is necessary for the appearance of stereotyped behaviors.     

Brain NADH and jumping behavior in the rat

The effects of either the reduced Nicotinamide Adenine Dinucleotide (NADH) microinjected into the brain or amphetamine injected peritoneally on jumping behavior were observed in 68 rats. The enhanced jumps in the group with amphetamine are the greatest among the three experimental groups. The enhanced effect of NADH microinjected into the caudate nucleus is stronger than those of NADH in the frontal cortex. The effects of extra NADH in the frontal cortex on the jumps are dose-dependent. NADH concentrations in the brain of rats with amphetamine increased immediately after behavioral procedure. The increased concentrations in the brain from both extra and intra sources are related to the enhanced jumps of rats.     

Do Dogs (Canis lupus familiaris) Make Counterproductive Choices Because They Are Sensitive to Human Ostensive Cues?

Dogs appear to be sensitive to human ostensive communicative cues in a variety of situations, however there is still a measure of controversy as to the way in which these cues influence human-dog interactions. There is evidence for instance that dogs can be led into making evaluation errors in a quantity discrimination task, for example losing their preference for a larger food quantity if a human shows a preference for a smaller one, yet there is, so far, no explanation for this phenomenon. Using a modified version of this task, in the current study we investigated whether non-social, social or communicative cues (alone or in combination) cause dogs to go against their preference for the larger food quantity. Results show that dogs' evaluation errors are indeed caused by a social bias, but, somewhat contrary to previous studies, they highlight the potent effect of stimulus enhancement (handling the target) in influencing the dogs' response. A mild influence on the dog's behaviour was found only when different ostensive cues (and no handling of the target) were used in combination, suggesting their cumulative effect. The discussion addresses possible motives for discrepancies with previous studies suggesting that both the intentionality and the directionality of the action may be important in causing dogs' social biases.     

A Systematic Review and Meta-Analysis of the Campylobacter spp. Prevalence and Concentration in Household Pets and Petting Zoo Animals for Use in Exposure Assessments

Animal contact is a potential transmission route for campylobacteriosis, and both domestic household pet and petting zoo exposures have been identified as potential sources of exposure. Research has typically focussed on the prevalence, concentration, and transmission of zoonoses from farm animals to humans, yet there are gaps in our understanding of these factors among animals in contact with the public who don’t live on or visit farms. This study aims to quantify, through a systematic review and meta-analysis, the prevalence and concentration of Campylobacter carriage in household pets and petting zoo animals. Four databases were accessed for the systematic review (PubMed, CAB direct, ProQuest, and Web of Science) for papers published in English from 1992–2012, and studies were included if they examined the animal population of interest, assessed prevalence or concentration with fecal, hair coat, oral, or urine exposure routes (although only articles that examined fecal routes were found), and if the research was based in Canada, USA, Europe, Australia, and New Zealand. Studies were reviewed for qualitative synthesis and meta-analysis by two reviewers, compiled into a database, and relevant studies were used to create a weighted mean prevalence value. There were insufficient data to run a meta-analysis of concentration values, a noted study limitation. The mean prevalence of Campylobacter in petting zoo animals is 6.5% based on 7 studies, and in household pets the mean is 24.7% based on 34 studies. Our estimated concentration values were: 7.65x10³cfu/g for petting zoo animals, and 2.9x10⁵cfu/g for household pets. These results indicate that Campylobacter prevalence and concentration are lower in petting zoo animals compared with household pets and that both of these animal sources have a lower prevalence compared with farm animals that do not come into contact with the public. There is a lack of studies on Campylobacter in petting zoos and/or fair animals in Canada and abroad. Within this literature, knowledge gaps were identified, and include: a lack of concentration data reported in the literature for Campylobacter spp. in animal feces, a distinction between ill and diarrheic pets in the reported studies, noted differences in shedding and concentrations for various subtypes of Campylobacter, and consistent reporting between studies.