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Differential down-regulation of D1-stimulated adenylate cyclase activity in rat forebrain after in vivo amphetamine treatments.

Amphetamine has complex behavioral actions in the rat that depend upon the release of dopamine in striatal and mesolimbic brain regions. To explore a possible role of the dopamine-sensitive cAMP second-messenger system in mediating these effects, we examined the effects of in vivo amphetamine treatments on the D1 receptor-coupled adenylate cyclase system in membranes from striatal and mesolimbic rat brain regions. The results show that amphetamine produces a regional, dose- and time-dependent down-regulation of adenylate cyclase activity. Intermediate and high doses of amphetamine (2.5 and 7.5 mg/kg, respectively), but not a low dose (1.0 mg/kg), resulted in a decrease in the apparent Vmax and/or an increase in the apparent Ka for the selective D1 partial agonist, SKF38393, in striatal membranes 30 min after amphetamine treatment. Treatment of rats with 7.5 mg/kg amphetamine for 30 and 60 min, but not 10 min, similarly resulted in a down-regulation of D1-mediated adenylate cyclase activity in striatal membranes. In contrast, in mesolimbic tissues, no amphetamine treatment at any time resulted in an alteration of SKF38393-stimulated adenylate cyclase activity relative to saline controls. The results of behavioral analyses also showed that animals exhibiting intense stereotypies had significantly lower striatal apparent Vmax values than did those animals engaged in moderate or no behavioral activity at the time of decapitation. These findings demonstrate that amphetamine treatments result in a down-regulation of striatal, but not mesolimbic, dopamine-sensitive adenylate cyclase activity that parallels the intense, stereotyped behaviors characteristic of dopaminergic activation in the striatum.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Alteration of striatal dopaminergic functions implicated in methamphetamine-induced reverse tolerance in rats.

Rats were injected repeatedly with methamphetamine (6 mg/kg per day, for 14 days). The effects of the repeated treatment on the change of behaviors and striatal DA metabolism induced by challenge with DA agonists were studied 10 days after the last injection. Repeated methamphetamine administration decreased the sedative effect of low dose apomorphine, and enhanced apomorphine-induced stereotyped behavior but reduced in after pretreatment with tetrabenazine. Striatal DA, HVA and DOPAC contents, and striatal gamma-butyrolactone-induced DA or DOPA accumulation were not altered by repeated methamphetamine treatment. The effect of apomorphine to decrease DA metabolite content and DA or DOPA accumulation was not changed either. As evidenced by experiments using alpha-MT, repeated methamphetamine administration increased DA utilization after methamphetamine or low dose apomorphine challenge, although it did not change DA utilization at the steady state (without drug challenge). These findings suggest that methamphetamine-induced reverse tolerance is accompanied by an increase of DA utilization resulting from the subsensitivity of DA utilization-modulating autoreceptors.

3,4-Dihydroxyphenylacetic Acid↗

A rat model of phencyclidine psychosis.

Phencyclidine (PCP)-induced behavior in rats was investigated in water maze and diving behavior tasks. The swimming and diving latencies of PCP-treated groups placed in a water maze apparatus were gradually shortened, and prolonged, respectively, while rats in a control group performed well. In all rats, stereotyped behavior and hyperlocomotion were absent. We propose that this animal model induced by lower doses of PCP may be useful for further studies to research schizophrenia.

Analysis of Variance↗

Quinelorane (LY163502), a D2 dopamine receptor agonist, acts centrally to facilitate penile erections of male rhesus monkeys.

The present study examined the effects of a specific D2 dopamine receptor agonist, quinelorane (LY163502), on male sexual responding of rhesus monkeys. The effects of quinelorane were assessed by observing the behavioral responses of male rhesus monkeys to a sexually receptive female monkey that they could see, hear, and smell, but not physically contact. Quinelorane (IM) treatment produced dose-dependent effects on male sexual responding. Penile erections and masturbation were markedly facilitated following treatment with either 2.5 or 5 micrograms/kg quinelorane. Higher doses of quinelorane (10 and 25 micrograms/kg) generally did not further augment sexual responding, but rather resulted in a return in sexual responding to control vehicle levels. Quinelorane had a biphasic effect on yawning behavior of the monkeys with low doses (2.5 and 5 micrograms/kg) facilitating yawning and high doses (25 micrograms/kg) inhibiting yawning. Quinelorane in the dose-range (1-25 micrograms/kg) being evaluated did not reliably influence stereotypic behavior. In order to determine whether quinelorane acts centrally or peripherally to stimulate male sexual behavior, the ability of the peripherally active dopamine antagonist, domperidone, and the centrally active dopamine antagonist, haloperidol, to block the facilitation of sexual behavior produced by quinelorane treatment was examined. Administration of domperidone (50-200 micrograms/kg) failed to block quinelorane's effects on sexual behavior, whereas treatment with haloperidol (5-20 micrograms/kg) prevented quinelorane from stimulating male sexual responding. These experiments provide further evidence that dopaminergic mechanisms may play a role in the regulation of male sexual behavior of rhesus monkeys and, in particular, demonstrate the sexual stimulant properties of agents that provide central stimulation to D2 dopamine receptor sites.

Animals↗

Subthalamic nucleus microinjections of 5-HT2 receptor antagonists suppress stereotypy in rats.

The subthalamic nucleus (STN) is an important mediator of basal ganglia output. We studied the effects of STN microinjections of the serotonin-2 (5-HT2) antagonists clozapine, mesulergine and M100,907 on apomorphine-induced stereotypic activity in the rat. Each compound profoundly decreased the expression of stereotypic behavior, with particularly strong effects to reduce gnawing behavior. Because M100,907 does not have appreciable affinity for dopamine D1 and D2 receptors, and since all three agents are 5-HT2 antagonists, the current data suggest that basal ganglia output related to orofacial movements can be significantly modified by 5-HT2 receptors. The results suggest that antipsychotics with serotonergic properties may have direct actions on the STN that influence their potential to produce orofacial and other motor side effects.

Animals↗

The effect of apomorphine on operant behavior in rats under normoxic and hypoxic conditions.

We studied the effect of apomorphine on the performance of rats, maintained on a free-operant shock-avoidance schedule under normoxic and hypoxic (12, 10, and 8% O2) environments. In a normoxic environment, apomorphine (1, 2, 4, and 8 mg/kg, i.p.) produced stereotyped behaviors and dose-dependent increases in the rats' lever-pressing response rate. In a hypoxic environment, however, the increase of the response rate induced by apomorphine at 1 mg/kg was suppressed by the hypoxic conditions tested. At a dose of 8 mg/kg apomorphine, it was also suppressed by exposure to severe hypoxia (10 and 8% O2). These results suggest that the impairment of avoidance behavior in rats by hypoxia was not always improved by apomorphine, and that the degree of improvement depends on the combined effects of the dosage of the drug injected, the degree of hypoxia, and the type of behavior observed.

Animals↗

Sonic and electric fish: at the crossroads of neuroethology and behavioral neuroendocrinology.

Field and laboratory studies of weakly electric and sound-producing teleost fishes demonstrate how steroidal and non-steroidal hormones mediate the translation of neural events into behavior. The development of this research program has depended upon an interdisciplinary neuroethological approach that has characterized the neurophysiological properties of the motor and sensory pathways that lead to the production and detection of easily quantified highly stereotyped behaviors, namely, electric organ discharges (EODs) and vocalizations. Neuroethological studies of these teleosts have now integrated a behavioral neuroendocrinology approach that has provided several examples of how hormone-sensitive neurobiological traits contribute to adaptive behavioral plasticity in natural habitats. As such, these studies provide guideposts for comparable studies in other groups of teleosts and vertebrates in general.

Androgens↗

Trimethylolpropane phosphate (TMPP) perfusion into the nucleus accumbens of the rat: electroencephalographic, behavioral and neurochemical correlates.

The infusion (0.13 mumol/infusion) of the convulsant trimethylolpropane phosphate (TMPP) into the nucleus accumbens (NA) of adults Sprague-Dawley rats reliably induced subclinical seizures, hyperlocomotor activity, and integrated stereotypies. Observation of these behaviors was temporally correlated with the appearance of EEG paroxysms, as well as with significant decreases in extracellular concentrations of both dopamine (DA) and norepinephrine (NE) in the NA. Repeated perfusion of TMPP revealed significant increases in stereotypic behavior during subsequent pre-drug baseline testing.

Animals↗

Task-related responses of monkey medullary dorsal horn neurons.

Medullary dorsal horn neurons with trigeminal sensory properties have been previously shown to have additional responses associated with cues relevant to the successful execution of a behavioral task. These "task-related" responses were evoked by environmental cues but were independent of the specific stimulus parameters. We have examined further the characteristics of task-related responses in medullary dorsal horn neurons of three monkeys. Single-unit activity was recorded while the monkeys were performing behavioral tasks that required them to discriminate thermal or visual stimuli for a liquid reward. Forty-five percent (34/75) of the medullary dorsal horn neurons studied exhibited task-related activity that was significantly correlated with the stereotypical behavioral events that occurred during the tasks. Similar events occurring outside of the task produced no response. In addition to the task-related activity of these medullary dorsal horn neurons, responses to mechanical and/or thermal stimuli presented within the neuron's receptive field were demonstrated in 28 of 34 cases. These sensory responses also were evoked by the same stimuli presented outside of the behavioral task. Fifteen of the neurons with task-related responses could be activated antidromically from thalamic stimulating electrodes. Task-related responses were categorized according to their relationship to the three phases of the behavioral trial: trial initiation, trial continuation, and trial termination. Although an individual task-related response was associated with a single behavioral event, most medullary dorsal horn neurons (30/34) exhibited a reproducible pattern of task-related responses that occurred during more than one phase of the trial. Trial-initiation task-related responses were subdivided depending on their correlation with specific events that occurred within that phase of the trial. One-third of the 18 excitatory trial-initiation responses were associated with the visual stimulus that cued the monkey to begin the trial; the remaining two-thirds were associated with the monkey's press of the button that actually initiated the trial. Trial-continuation task-related responses (observed while the monkey waited for a thermal stimulus that triggered a rewarded motor response) were shown to be independent of the actual temperature of the thermal stimulus. In addition these trial-continuation task-related responses were also noted during trials without a thermal stimulus, in which the trigger cue was the onset of a light (in a visual task).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Cleaner shrimp use a rocking dance to advertise cleaning service to clients.

Signals transmit information to receivers about sender attributes, increase the fitness of both parties, and are selected for in cooperative interactions between species to reduce conflict [1, 2]. Marine cleaning interactions are known for stereotyped behaviors [3-6] that likely serve as signals. For example, "dancing" and "tactile dancing" in cleaner fish may serve to advertise cleaning services to client fish [7] and manipulate client behavior [8], respectively. Cleaner shrimp clean fish [9], yet are cryptic in comparison to cleaner fish. Signals, therefore, are likely essential for cleaner shrimp to attract clients. Here, we show that the yellow-beaked cleaner shrimp [10] Urocaridella sp. c [11] uses a stereotypical side-to-side movement, or "rocking dance," while approaching potential client fish in the water column. This dance was followed by a cleaning interaction with the client 100% of the time. Hungry cleaner shrimp, which are more willing to clean than satiated ones [12], spent more time rocking and in closer proximity to clients Cephalopholis cyanostigma than satiated ones, and when given a choice, clients preferred hungry, rocking shrimp. The rocking dance therefore influenced client behavior and, thus, appears to function as a signal to advertise the presence of cleaner shrimp to potential clients.

Analysis of Variance↗

Psychobiological risk factors for vulnerability to psychostimulants in human adolescents and animal models.

Adolescence is associated with an increased risk of developing drug abuse/dependence. During this ontogenetic phase, brain and hormonal systems are still undergoing crucial maturational rearrangements, which take place together with significant modifications in psychosocial development. However, the neurohormonal and behavioral facets of adolescence have been poorly investigated in relation to the vulnerability to psychostimulants such as MDMA ("Ecstasy") and amphetamine (AMPH). Novelty-seeking, a temperamental/behavioral trait that is typical of this age period, might substantially contribute to both psychological and psychobiological vulnerability. In humans, an elevated score of novelty-sensation seeking and a derangement of monoaminergic function were both associated with late adolescence MDMA users compared to controls. In animal models of periadolescence, the search for novel stimuli and sensations actually shares a common neurobiological substrate (the reward-related brain mesolimbic pathways) with psychostimulants. The present review summarises recent work in mice, which indicates that periadolescent subjects are characterized by an unbalanced and "extremes-oriented" behavior and by elevated novelty-seeking compared to adults. Repeated and intermittent administration of cocaine or AMPH was associated with the development of a prominent locomotor sensitization in periadolescents, which failed to exhibit the marked sensitization of the stereotyped behavioral syndrome--possibly associated with poor welfare--that was typical of adults. A unique profile of integrated behavioral and physiological hyporesponsivity to both forced novelty and acute AMPH administration during periadolescence was also found. As a whole, these results, together with previous work on this topic, suggest that periadolescents may be more "protected" from AMPH-related aversive properties, and perhaps more vulnerable to the experience of internal states of reward, than older animals. Thus, the present animal model of adolescence seems to represent a reliable and useful method for the investigation of vulnerability to a variety of habit-forming agents or emotional experiences whose positive reinforcing properties may rely on common neurobiological substrates. A deeper understanding of psychostimulant effects during adolescence on the complex interaction between genetic, neurobiologic, psychosocial, and environmental factors will lead to earlier and more effective prevention and treatment.

Adolescent↗

Two types of dopamine receptors in behavioral regulation.

Evidence has been presented indicating the existence of distinct dopamine receptors in the brain. The experimental proof that two types of dopamine receptors--the excitation-mediating (DAe) receptors and the inhibition-mediating (DAi) receptors--exist in the snail brain is put forward. The functioning of DAi and DAe receptors in locomotor activity and stereotyped behavior is discussed along with implications of dopaminergic involvement in a gratification system.

Animals↗

Effects of benzoylecgonine on the behavior of suckling rats: a preliminary report.

A major metabolite of cocaine, benzoylecgonine, causes behavioral activation that progresses to seizures when given intraventricularly to 2-week-old rats. The seizures are characterized by running, hopping, and vocalizing and are mixed with shorter-duration tonic episodes. Pretreatment with haloperidol, at a dose aimed at blocking stereotyped behavior, did not suppress these behaviors. In contrast, seizures were prevented by antiepileptic drugs, with the order of potency being diazepam greater than phenobarbital greater than phenytoin. We hypothesize that the long-lasting cocaine metabolite, benzoylecgonine, contributes to the infant cocaine intoxication syndrome.

Animals↗

Wasp manipulates cockroach behavior by injecting venom cocktail into prey central nervous system.

The parasitoid wasp Ampulex compressa induces behavioral changes in the cockroach prey by injecting venom into its central nervous system. In contrast to most other venomous predators, the wasp's sting does not induce paralysis. Rather, the two consecutive stings in the thoracic and head ganglia induce three stereotypic behavioral effects. The prey behavior is manipulated in a way beneficial to the wasp and its offspring by providing a living meal for its newborn larva. The first sting in the thorax causes a transient front leg paralysis lasting a few minutes. This paralysis prevents the cockroach from fighting with its front legs, thereby facilitating the second sting in the head. A postsynaptic block of central synaptic transmission mediates this leg paralysis. Following the head sting, dopamine identified in the venom induces 30 minutes of intense grooming that appears to prevent the cockroach from straying until the last and third behavioral effect of hypokinesia commences. In this lethargic state that lasts about three weeks, the cockroach does not respond to various stimuli nor does it initiates movement. However, other specific behaviors of the prey are unaffected. We propose that the venom represses the activity of head ganglia neurons thereby removing the descending excitatory drive to specific thoracic neurons.

Action Potentials↗

Acute pharmacological activity of intravenous cocaine in the rhesus monkey.

The effects of the intravenous administration of cocaine (0.05-5.0 mg/kg) on body temperature, heart rate, respiration rate and several unconditioned behavioral categories were ascertained in unanesthetized male rhesus monkeys. Statistically significant increases in body temperature, respiration rate and heart rate occurred only after the largest dosage tested. Subjective increases in pupil size, activity, reactivity and vocalization as well as the occurrence of stereotyped behaviors, mydriasis and refusal to ingest fruit, were observed following injection with 0.2, 0.5 mg/kg and 5.0 mg/kg. A large degree of consistent intersubject variability in the magnitude of these responses was present. There was no consistent correlation across subjects between the magnitude of these responses and the plasma level of cocaine. However, within a given subject a direct correlation existed between these parameters.

Animals↗

Behavioral and hormonal effects of attachment object separation in surrogate-peer-reared and mother-reared infant rhesus monkeys.

Mother-reared and surrogate-peer-reared rhesus monkeys were separated from their respective attachment objects at 6 months of age and tested for the following 9 weeks to determine their home-cage behavior and their pituitary-adrenocortical responses to stress. Both groups displayed a strong immediate behavioral response to separation which was characterized by increased vocalization, increased locomotion, and decreased self-play. However, the surrogate-peer-reared infants showed a subsequent recovery in their levels of self-play whereas the mother-reared infants instead developed stereotypic behavior patterns such as repetitive pacing. The 2 groups displayed similar plasma cortisol responses to weekly sessions in an apparatus equipped with animated toy "monsters". Mother-reared but not surrogate-peer-reared subjects, however, also manifested elevated cortisol levels when an animal in an adjacent cage was captured and removed for stress testing. Mother-reared infant monkeys thus responded in a stronger and more prolonged manner to the loss of their attachment object than surrogate-peer-reared infants. These results suggest that infant rhesus monkeys form stronger attachments to monkey mothers than to inanimate surrogate mothers, a phenomenon which has not been as clearly demonstrated using other indices of attachment strength.

Animals↗

Further localization of cardiovascular and behavioral actions of substance P in the rat brain.

Cardiovascular and behavioral actions of substance P (SP) were examined after microinjection into the medial preoptic area (MPO), anterior hypothalamic area (AH), and ventral tegmental area (VTA) in conscious unrestrained rats. SP elicited marked increases in mean arterial pressure and heart rate as well as stereotyped behaviors of excessive grooming and exploring when injected into the MPO or AH. In the MPO, the latencies to the cardiovascular responses were observed after SP injection into the VTA. These results, together with our previous results, suggest that SP acts as transmitter or modulator in the rostral hypothalamic areas to elicit cardiovascular defense responses. In contrast, SP may not be involved in causing a defense reaction in the more caudal areas of the defense center.

Animals↗

Cross-validation of the factor structure of the Aberrant Behavior Checklist for persons with mental retardation.

The original factor structure of the Aberrant Behavior Checklist was cross-validated with an American sample of 470 persons with moderate to profound mental retardation, including nonambulatory individuals. The results of the factor analysis with varimax rotation essentially replicated previous findings, suggesting that the original five factors (Irritability, Lethargy, Stereotypic Behavior, Hyperactivity, and Inappropriate Speech) could be cross-validated by factor loadings of individual items. The original five scales continue to show high internal consistency. These factors are easily interpretable and should continue to provide valuable research and clinical information.

Adult↗