Permissive role of D-1 receptor stimulation for the expression of D-2 mediated behavioral responses: a quantitative phenomenological study in rats

The syndrome of behavioral stimulation induced in male Sprague-Dawley rats by two dopaminergic agents was studied by distinguishing specific behavioral items and quantifying them in terms of their incidence. The specific D-2 agonist LY 171555 elicited yawning, genital grooming, exploratory behavior, downward sniffing and licking but failed to induce gnawing even at high doses. On the other hand, the D-1/D-2 agonist apomorphine elicited the full stereotyped syndrome including gnawing. Depletion of endogenous dopamine (DA) by alpha-methyltyrosine (alpha-MT) prevented the ability of LY 171555 to elicit all the items of behavioral stimulation including the stereotyped ones (sniffing and licking). In contrast, the ability of apomorphine to induce stereotypies was not reduced by depletion of endogenous DA by alpha-MT pretreatment. Blockade of D-1 receptors with SCH 23390 abolished the capacity of both LY 171555 and apomorphine to elicit all the items of behavioral stimulation. In alpha-MT pretreated rats, administration of low doses of the D-1 agonist SKF 38393 (2.5 mg/kg s.c.) reinstated the ability of LY 171555 to elicit behavioral stimulation and eventually conferred the ability of inducing gnawing. The results support the hypothesis that stimulation of D-1 receptors exerts a permissive role for the expression of behavioral stimulation following D-2 receptor stimulation. Endogenous DA appears to provide sufficient D-1 input to permit full expression of yawning, genital grooming, exploratory behavior, downward sniffing and licking following D-2 stimulation; pharmacological stimulation of D-1 in addition to D-2 receptors seems however necessary for full expression of the highest rank stereotypy item, gnawing.     

Phencyclidine-induced stereotyped behavior and serotonergic syndrome in rat

Phencyclidine (50 mg/kg, i.p.) induced in rats a biphasic response consisting of serotonergic syndrome followed by stereotyped behavior. The initial serotonergic syndrome was significantly reduced by cinanserin (20 mg/kg, i.p.) and cyproheptadine (2.0 mg/kg, i.p.) but not influenced by haloperidol (0.5 mg/kg, i.p.). The later stereotyped behavior was significantly reduced by haloperidol (0.5 mg/kg, i.p.) but not influenced by cinanserin (20 mg/kg, i.p.) or cyproheptadine (2.0 mg/kg, i.p.). A lower dose of phencyclidine (5.0 mg/kg, i.p.) elicited only haloperidol-sensitive stereotyped behavior. These results indicate that serotonergic and dopaminergic mechanisms may mediate the behavioral effects of phencyclidine in rats.     

Evidence that the nigrotegmental GABAergic projection mediates stereotypy induced by apomorphine and intranigral muscimol

The substantia nigra plays a pivotal role in the relay of output from the striatum. One neural pathway from substantia nigra projects GABAergic fibers to the caudal mesencephalic tegmentum, terminating in the vicinity of the pedunculopontine nucleus (PPN). To evaluate the functional importance of this projection in the mediation of stereotyped behaviors of striatal and nigral origin, we microinjected low doses of the GABA agonist, muscimol, bilaterally into the vicinity of the PPN. This muscimol treatment resulted in a total blockade of all stereotyped behaviors normally elicited by systemic apomorphine or by intranigral muscimol. Blockade was not observed in animals microinjected with muscimol into the dorsal reticular formation, 1 mm above the level of the PPN. Our results indicate that the nigrotegmental projection may play a crucial role in the expression of stereotyped and dyskinetic behaviors of basal ganglia origin.     

Corticotropin releasing factor induces anxiogenic locomotion in trout and alters serotonergic and dopaminergic activity

Corticotropin releasing factor (CRF) and serotonin (5-HT) are strongly linked to stress and anxiety in vertebrates. As a neuromodulator in the brain, CRF has anxiogenic properties often characterized by increased locomotion and stereotyped behavior in familiar environments. We hypothesized that expression of anxiogenic behavior in response to CRF will also be exhibited in a teleost fish. Rainbow trout were treated with intracerebroventricular (icv) injections of artificial cerebrospinal fluid (aCSF), 500 or 2000 ng ovine CRF, or not injected. Treatment with either dose of CRF elicited greater locomotion and pronounced head shaking behavior but did not influence water column position. Locomotor and head shaking behaviors may be analogous to the increased stereotypy evoked by icv CRF in rats and may reflect the expression of stress/anxiety behavior. Injection with either aCSF or CRF produced significant increases in plasma cortisol. The absence of behavioral changes in aCSF-injected fish suggests that the behavioral responses following CRF were not due to cortisol. Treatment with 2000 ng CRF significantly increased serotonin, 5-HIAA and dopamine concentrations in the subpallium and raphé and increased 5-HIAA in the preoptic hypothalamus (POA). Concurrent effects of CRF on central monoamines, locomotion and head shaking in trout suggest that anxiogenic properties of CRF are evolutionarily conserved. In addition, positive linear correlations between locomotion and serotonergic and dopaminergic function in the subpallium, POA and raphé nuclei suggest a locomotory function for these monoamines.     

Corticotropin releasing factor induces anxiogenic locomotion in trout and alters serotonergic and dopaminergic activity

Corticotropin releasing factor (CRF) and serotonin (5-HT) are strongly linked to stress and anxiety in vertebrates. As a neuromodulator in the brain, CRF has anxiogenic properties often characterized by increased locomotion and stereotyped behavior in familiar environments. We hypothesized that expression of anxiogenic behavior in response to CRF will also be exhibited in a teleost fish. Rainbow trout were treated with intracerebroventricular (icv) injections of artificial cerebrospinal fluid (aCSF), 500 or 2000 ng ovine CRF, or not injected. Treatment with either dose of CRF elicited greater locomotion and pronounced head shaking behavior but did not influence water column position. Locomotor and head shaking behaviors may be analogous to the increased stereotypy evoked by icv CRF in rats and may reflect the expression of stress/anxiety behavior. Injection with either aCSF or CRF produced significant increases in plasma cortisol. The absence of behavioral changes in aCSF-injected fish suggests that the behavioral responses following CRF were not due to cortisol. Treatment with 2000 ng CRF significantly increased serotonin, 5-HIAA and dopamine concentrations in the subpallium and raphé and increased 5-HIAA in the preoptic hypothalamus (POA). Concurrent effects of CRF on central monoamines, locomotion and head shaking in trout suggest that anxiogenic properties of CRF are evolutionarily conserved. In addition, positive linear correlations between locomotion and serotonergic and dopaminergic function in the subpallium, POA and raphé nuclei suggest a locomotory function for these monoamines.     

Behavioral effects of phencyclidine (PCP) in the dog: A possible animal model of PCP toxicity in humans

The acute behavioral effects of PCP, given intravenously in doses of .25, .50, 1.00, 2.50 and 5.00 mg/kg, were examined in 8 male mongrel dogs tested in an open field arena. All doses produced an initial “eyes open” coma accompanied by tremors, rigidity, jerky limb movements, nystagmus, excessive salivation, head weaving, stiff tail, and stereotyped sniffing. In addition, doses of 1.0 mg/kg and above produced jaw snapping, opisthothonus and clonic/tonic seizures. Following recovery from coma, animals evinced pronounced hyperactivity and stereotyped circling. In contrast to other laboratory animal species, the behavioral effects produced by PCP in the dog are strikingly similar to those reported to occur in humans after PCP administration, suggesting that this species may provide an excellent laboratory animal model for studying PCP toxicity.     

兴隆山自然保护区麝场圈养马麝刻板行为的比较

于2001年3月—2002年1月,采用焦点取样法对甘肃兴隆山自然保护区麝场圈养马麝的刻板行为进行了研究。结果表明:该麝场的圈养马麝有刻板行为的发育,雌麝的刻板行为持续时间少于雄麝,但二者间的差异不显著。野捕马麝幼年期的人工哺乳经历使其刻板行为表达强度相对小于麝场圈养下繁殖马麝。年龄对雌雄麝的刻板行为表达强度的效应相似,亚成体马麝的刻板行为表达较多,成体马麝体的刻板行为表达相对较少,老年马麝刻板行为持续时间最长,2.5和4.5岁是圈养马麝刻板行为发育的关键时期。此外,能顺利繁殖的个体,其刻板行为表达的持续时间少于繁殖失败的个体。     

Cholecystokinin modulation of apomorphine- or amphetamine-induced stereotypy in rats: opposite effects.

Stereotyped behavior can be induced by the dopamine agonist apomorphine or by the releasing agent amphetamine. Cholecystokinin influence on dopamine-mediated behaviors has been extensively studied but a real controversy remains. Our purpose was to further characterize the dopamine-cholecystokinin interaction in apomorphine- and amphetamine-induced stereotyped behavior using sulphated cholecystokinin octapeptide (CCK8) and cholecystokinin tetrapeptide (CCK4) treatments. The results showed that CCK8 decreases apomorphine-induced stereotyped behavior and CCK4 has no effect. CCK4 and CCK8 increased the amphetamine-induced stereotyped behavior; CCK4 was more effective. The results confirm the opposite modulation of apomorphine or amphetamine-induced stereotyped behavior by CCK. These data suggest that this modulation is mediated by both CCK receptors on apomorphine-induced and only by CCK(2) receptors on amphetamine-induced stereotyped behavior.     

Reverse tolerance to stimulant-induced abnormal behavior

Changes in the behavior of female rats induced by repeated, daily administrations of d-amphetamine or cocaine were determined in two experiments. Potentiation of stereotyped behavior in the initial post-injection period, which suggests a decrease in the latency to reach maximum stereotyped behavior, was found during and following daily treatment with both drugs. In addition, the maximum level of stereotyped behavior was increased during and following treatment with cocaine. In two experiments, behavior induced by apomorphine was potentiated during the initial post-injection period following a course of repeated, daily administrations of d-amphetamine or cocaine, suggesting the development of supersensitive dopaminergic post-synaptic mechanisms.     

Behavioral studies on the enantiomers of butaclamol demonstrating absolute optical specificity for neuroleptic activity.

Butaclamol is a member of a new chemical class for which antipsychotic activity in humans has been demonstrated. Butaclamol, a racemate, has been resolved into its optical isomers and a separation of activities was found to occur between the (+) and (-) enantiomers. The present experiments show that at doses ranging from 0.1 to 0.3 mg/kg the (+) enantiomer abolished amphetamine-induced (a) stereotyped behavior and (b) rotational behavior in rats with unilateral lesions in the substantia nigra. It also inhibited the lever-pressing response in the continuous (Sidman) avoidance procedure, blocked discriminated avoidance behavior, and decreased ambulation and rearing in the open field. In contrast, the (-) enantiomer was devoid of behavioral activity at 100-500 times larger doses. At considerably higher doses (+)-butaclamol antagonized epinephrine-induced mortality. Again, the (-)-butaclamol was devoid of this activity as well. The significance of absolute optical specifity manifested by a neuroleptic drug is discussed in the light of dopaminergic and adrenergic mechanisms.     

Influence of imidazole on behavioral effects induced by dopaminergic agonists in rats

Imidazole (IMI) (from 18.7 to 300 mg/Kg) i.p. injected in adult rats induced shaking, which was antagonized by both morphine (MOR) and haloperidol (HALO) but not by methysergide (MET). I.p. IMI pretreatment inhibited the penile erections (PE) and stretching and yawning (SY) typically elicited by N-n-propylnorapomorphine (NPA), a well-known CNS dopamine (DA) receptor stimulant, injected either i.p. or i.c.v., whereas it enhanced stereotyped behavior (SB). IMI had similar effects on the same parameters considered when injected before lisuride, an ergot derivative also active as a central DA receptor agonist. In this case not only SB but also and above all aggressiveness were markedly potentiated, both the signs appearing at doses of lisuride which were "per se" ineffective. Aggressiveness, like SB, was not sex linked and was antagonized by HALO and MOR, but not by MET. IMI alone potentiated the fighting induced by electrical shock, an effect which was abolished by HALO pretreatment. Considering the results obtained as a whole it is submitted that IMI antagonizes PE and SY through a selective blockade of a class of DA receptors, presumably DA presynaptic autoinhibitors, thus potentiating SB and aggressiveness, which involve stimulation of DA postsynaptic receptors.     

The effect of housing and environmental enrichment on stereotyped behavior of adult vervet monkeys (Chlorocebus aethiops)

Little information is available on the response of vervet monkeys to different housing conditions or on the suitability of enrichment devices or methods for vervet monkeys. In this study, the authors evaluated the occurrence of stereotyped behavior in adult vervet monkeys under various conditions of housing and enrichment. The variables included cage size, cage level (upper or lower), enrichment with a foraging log, enrichment with an exercise cage and presence of a mate. The authors first determined the incidence of stereotyped behavior in captive-bred, singly housed adult female and male vervet monkeys. They then exposed monkeys to different housing and enrichment situations and compared the incidence of stereotyped behavior among the monkeys. The authors found that more females than males engaged in stereotyped behavior and that females, on average, engaged in such behavior for longer periods of time than males. Stereotyped behavior was most often associated with a small, single cage. The average amount of observed stereotyped activity in monkeys housed in a small cage was significantly lower when the monkeys had access to either a foraging log or an exercise cage. Stereotyped behavior was also lower in female monkeys that were housed (either with a male or without a male) in a larger cage. The least amount of abnormal behavior was associated with the largest, most complex and enriched housing situation. Males and females housed in cages on the lower level of two-level housing engaged in more stereotyped behavior than did monkeys housed in the upper level, regardless of the presence or type of enrichment provided.     

Delay in formation of phenamine tolerance after epiphysectomy in rats

Amphetamine-induced stereotyped behavior is a nonsteady oscillatory process with minute fluctuations rate of head turnings. After acute amphetamine stereotypy have lower amplitude and limited rhythmicity in pinealectomized rats as compared with intact animals. Pinealectomy also delayed tolerance after chronic administration of amphetamine (5 mg/kg/day, 14 days) without usual decrease number of short period (2-3 min) fluctuations in time course of stereotypy.     

Hormonal control of invertebrate behavior

Invertebrates show a wide variety of behaviors that are influenced by hormones. In insects the involvement of hormones at a particular life stage is directly correlated with the complexity of the behavioral repertoire at that stage. In larval stages, the steroid hormone, ecdysone, when present with juvenile hormone, apparently causes the behaviors observed during the periodic molts. At the end of larval life, ecdysone in the absence of juvenile hormone triggers the onset of premetamorphic behaviors such as wandering behavior and cocoon-spinning behavior. In insects having complete metamorphosis, the emergence (eclosion) of the adult from the pupal case is accomplished by a stereotyped program of movements that are triggered by a peptide hormone. In moths, injection of this “eclosion hormone” into competent recipients will cause the release of the eclosion program. Also this program can be elicited by the hormone from the isolated abdominal central nervous system (CNS). The onset of reproductive behavior in females of various species requires juvenile hormone. In addition, certain peptides are then involved in the transition from virgin to mated behaviors. Also, pupatitive peptide factors trigger specific stereotyped behaviors such as those involved in mate attraction and in oviposition. In males, the control is simpler. Juvenile hormone is required for the maturation of sexual behavior in only a few species. But in at least one insect group, the cockroaches, a neurosecretory hormone serves to release directly copulatory behavior. Social behavior and migratory behavior in certain insects are also under hormonal influence. Hormones play a prominent role in regulating the behavior of gastropod mollusks. The best studied examples involve the hormonal stimulation of egg-laying behavior by CNS peptides. Also, peptide hormones cause stereotyped changes in specific identified neurons in the CNS of various gastropods. In at least some cases, these latter changes are related to arousal from aestivation.With their simple nervous systems, invertebrates are especially suited for studies on the mode of action of hormones on the nervous system. In most cases the behavioral effects of these hormones appear to be due to their direct action on the CNS. Indeed, the isolated moth CNS will respond to the eclosion hormone by generating the motor program that gives rise to the emergence behavior, and various isolated molluscan preparations will respond to hormones with stereotyped neural responses. By the direct application of hormone to the surface of identified nerve cells in mollusks it has been possible to localize target cells for specific hormones. Little is known of the mode of action of ecdysone or juvenile hormone in altering behavior. Peptide hormones appear to have effects which long outlast the actual presence of the hormone. In at least two cases, cyclic AMP has been implicated as a mediator of the hormonal response.     

Opioid peptides within the midbrain periaqueductal gray suppress affective defense behavior in the cat

The effects of the methionine-enkephalin analog [D-Ala2-Met5]-enkephalinamide (DAME) upon the threshold for affective defense behavior were determined following microinjections placed into midbrain periaqueductal gray sites from which this response was elicited. Affective defense behavior was elicited by electrical stimulation through a cannula electrode situated in the dorsal aspect of the midbrain periaqueductal gray. Dose-response curves characterizing the effects of DAME upon affective defense behavior were determined utilizing the following doses: 0.25, 0.5 and 1.0 microgram in 0.5 microliter saline, pH = 7.4 or vehicle control (saline). Response thresholds were tested 10-30, 30-60, 60-90, 120-150, 180-210, 1440-1470 and 2880-2910 min postinjection. The results obtained indicated that injections of DAME at a dose of 1.0 microgram/0.5 microliter produced significant, long duration elevations in affective defense thresholds, lasting up to 1440-1470 min postinjection. Lower doses of DAME (0.25 and 0.5 microgram/0.5 microliter) also resulted in significant increases in affective defense thresholds, but these effects were of shorter durations (60-90 and 120-150 min) postinjection, respectively. The suppressive effects of DAME were blocked when animals were pretreated with naloxone (10 micrograms/0.5 microliter) microinjected into the same midbrain periaqueductal gray site into which 0.25 microgram DAME was injected and affective defense behavior was elicited.     

圈养马麝刻板行为表达与粪样类固醇激素的关系

2017年7月1日-8月31日及2018年6月1日-7月31日,在甘肃兴隆山保护区马麝繁育中心,采用焦点取样法和连续记录法进行了圈养马麝的刻板行为取样,采集同期粪样,并用放射免疫分析法（RIA）检测粪样中肾上腺皮质醇、睾酮及雌二醇激素的水平,分析了圈养马麝刻板行为表达与上述3种激素水平的关系。结果显示,展现刻板行为的圈养马麝的皮质醇水平（111.099 ± 16.231）ng/g略高于无刻板行为表达的马麝（95.640± 9.738） ng/g,差异未达显著（P> 0.05）;展现刻板行为雄麝的睾酮水平（135.900± 21.582）ng/g略高于无刻板行为的雄麝（108.182 ± 9.689） ng/g,差异也不显著（P> 0.05）;展现刻板行为雌麝的雌二醇水平（0.445 ± 0.116）ng/g显著低于无刻板行为雌麝（10.843 ± 1.142）ng/g（P< 0.05）。研究结果表明,圈养雄性马麝的刻板行为表达与其类固醇激素水平不相关;而雌麝的刻板行为表达与雌二醇分泌显著负相关,这与其繁殖及健康状况有关。在麝类驯养实践中,可将粪样类固醇激素水平（尤其是雌二醇）作为其受胁迫水平及行为健康的监测指标。     

Cholinergic induction of seizures in the rat prefrontal cortex

Intracerebral microinjection of the cholinergic agonist, carbachol, into the medial prefrontal cortex of the rat, induced a profound behavioral syndrome consisting of repetitive, stereotyped forepaw treading in an upright posture. Electroencephalographic analysis revealed multiple bursts of sharp waves, 200-300 microV, accompanying the carbachol-elicited motor behavior. Pretreatment with intraperitoneal doses of three anticonvulsant drugs, clonazepam, diazepam, and pentobarbital, blocked the manifestation of the motor behavior. These observations suggest that activation of cholinergically innervated regions of the rat medial prefrontal cortex induces an atypical form of seizures.     

Effect of feeding boxes on the behavior of stereotyping amur tigers (Panthera tigris altaica) in the Zurich Zoo,Zurich, Switzerland

The stereotyped pacing shown by the two Amur tigers in the Zurich Zoo was hypothesized as being caused by permanently frustrated appetitive foraging behavior. Several electrically controlled feeding boxes were installed and access to each box was possible only twice a day for 15 min at semi‐random times. The boxes had to be opened actively by the tigers. Two trials were carried out: one with solitary confinement, and one with paired confinement. During box feeding, the female's stereotyped pacing was significantly reduced from 16% (solitary confinement, conventional feeding) and 7% (paired confinement, conventional feeding) to 1% (solitary confinement) and less than 0.01% (paired confinement) of the daily observed time. The female's sleeping increased significantly in both solitary and paired confinement. The male only showed a significant reduction in stereotyped pacing behavior when kept with the female (conventional feeding: 10%; box feeding: <0.01% of the daily observed time). On days with a box‐feeding regime in paired confinement, the male spent 25% (83 min) of the observed time with active behavior at the feeding boxes. The results support the hypothesis that permanently frustrated appetitive foraging behavior causes stereotyped pacing in adult tigers. Zoo Biol 21:573–584, 2002. © 2002 Wiley‐Liss, Inc.     

Orienting responses and vocalizations produced by microstimulation in the superior colliculus of the echolocating bat, Eptesicus fuscus

An echolocating bat actively controls the spatial acoustic information that drives its behavior by directing its head and ears and by modulating the spectro-temporal structure of its outgoing sonar emissions. The superior colliculus may function in the coordination of these orienting components of the bat's echolocation system. To test this hypothesis, chemical and electrical microstimulation experiments were carried out in the superior colliculus of the echolocating bat, Eptesicus fuscus, a species that uses frequency modulated sonar signals. Microstimulation elicited pinna and head movements, similar to those reported in other vertebrate species, and the direction of the evoked behaviors corresponded to the site of stimulation, yielding a map of orienting movements in the superior colliculus. Microstimulation of the bat superior colliculus also elicited sonar vocalizations, a motor behavior specific to the bat's acoustic orientation by echolocation. Electrical stimulation of the adjacent periaqueductal gray, shown to be involved in vocal production in other mammalian species, elicited vocal signals resembling acoustic communication calls of E. fuscus. The control of vocal signals in the bat is an integral part of its acoustic orienting system, and our findings suggest that the superior colliculus supports diverse and species-relevant sensorimotor behaviors, including those used for echolocation.     

Factors influencing stereotyped behavior of primates in a zoo

Stereotyped behavior is the uniform repetition of a motor pattern that occurs at a higher frequency than considered typical for a species when observed in a natural environment. Stereotypies may be considered atypical behavior and usually indicate that an animal's psychological welfare is at a suboptimal level. Instantaneous scans at 30-sec intervals during 20-min observation periods were conducted on eight primate species at the St. Louis Zoo to determine frequency of occurrence of stereotyped behavior. Results indicated that many biotic and abiotic factors were related to the frequency of stereotyped behavior by captive primates, although rearing method was more important than present environmental conditions. © 1994 Wiley-Liss, Inc.