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PubMed1986

Evidence for multiple opiate receptor involvement in different phencyclidine-induced unconditioned behaviors in rats.

Rats were used for comparing the behavioral response profiles of phencyclidine (PCP) and d,1-N-allylnormetazocine (NANM), two drugs that are proposed to exert their effects through the "PCP/sigma" receptor. Phencyclidine (1.0-5.0 mg/kg) and NANM (2.5-10.0 mg/kg) induced dose-related increases in locomotion, sniffing, repetitive head movements, non-object directed mouth movements, and ataxia. Both drugs also increased food and water consumption during the latter portion of the drug response. Ingestive behaviors induced by PCP (2.5 mg/kg), as with eating and drinking stimulated by the mu-opiate morphine (2.0 mg/kg), were blocked by a relatively low dose of the opiate antagonist naloxone (0.5 mg/kg). Multiple injections of PCP (2.5 mg/kg for 4 days) or NANM (10.0 mg/kg for 4 days) augmented several measures of behavioral activation, including horizontal locomotion, rearing, and nonfocused sniffing, but did not significantly change stereotyped behaviors or ataxia. Reciprocal cross-sensitization of locomotor activation is indicated by the finding that the response to a challenge injection of PCP (2.5 mg/kg) or to NANM (10.0 mg/kg) after 4 days of treatment with the other drug closely resembled the enhanced locomotor response observed after the chronic treatment. Phencyclidine and NANM thus appear to exert many of their effects on unconditioned behavior through common mechanisms, including interaction with sigma receptors. In addition, these findings are consistent with previous suggestions that a mu-opiate receptor system may modulate some effects of PCP.

Animals↗

PubMed1987

Effects of D2-dopaminergic receptor stimulation on male rat sexual behavior.

The effects of selective D2-dopaminergic receptor stimulation with LY163502 on male rat copulatory behavior were evaluated. LY163502 (25 ng/kg to 25 micrograms/kg s.c.) produced increases in the percentage of sexually inactive rats displaying mounting behavior and ejaculating during the test period. Within this same dose range, LY163502 administration induced an increase in the percentage of non-ejaculator rats that were capable of ejaculation. These findings are viewed as evidence that LY163502 can initiate sexual behavior and lower the threshold for ejaculation. The effects of LY163502 were further evaluated in rats that were capable of ejaculation during the test period. LY163502 (25 ng/kg to 25 micrograms/kg s.c. or p.o.) induced significant reductions in ejaculatory latency. These effects were blocked by prior treatment with centrally active dopaminergic antagonists, RO 22-1319 and sulpiride, but not with a peripherally active antagonist, domperidone. LY163502 administration was also found to inhibit sexual behavior in low doses of 25 pg/kg-10 ng/kg s.c. and in a much larger dose of 25 mg/kg s.c. These inhibitory effects are viewed as behavioral manifestations of selective dopaminergic autoreceptor activation with low doses and as the disruption of sexual behavior by induction of intense stereotypic behavior with high doses.

Administration, Oral↗

PubMed2006

Electrical stimulation of the pedunculopontine tegmental nucleus in freely moving awake rats: time- and site-specific effects on two-way active avoidance conditioning.

The pedunculopontine tegmental nucleus (PPTg) is involved in the regulation of thalamocortical transmission and of several functions related to ventral and dorsal striatal circuits. Stimulation of the PPTg in anesthetized animals increases cortical arousal, cortical acetylcholine release, bursting activity of mesopontine dopaminergic cells, and striatal dopamine release. It was hypothetized that PPTg stimulation could improve learning by enhancing cortical arousal and optimizing the activity of striatal circuits. We tested whether electrical stimulation (ES) of the PPTg, applied to freely-moving awake rats previously implanted with a chronic electrode, would improve the acquisition and/or the retention of two-way active avoidance conditioning, and whether this effect would depend on the specific PPTg region stimulated (anterior vs posterior) and on the time of ES: just before (pre-training) or after (post-training) each of three training sessions. The treatment consisted of 20 min of ES (0.2 ms pulses at 100 Hz; current intensity: 40-80 microA). The results showed that (1) this stimulation did not induce either any signs of distress nor abnormal behaviors, apart from some motor stereotyped behaviors that disappeared when current intensity was lowered; (2) pre-training ES applied to the anterior PPTg improved the acquisition of two-way active avoidance, (3) no learning improvement was found after either post-training ES of the anterior PPTg, or pre- and post-training ES of the posterior PPTg. The results give support to a role of PPTg in learning-related processes, and point to the existence of functional PPTg regions.

Analysis of Variance↗

PubMed2004

Involvement of the sigma1 receptor in the appetitive effects of cocaine.

Cocaine induces in the brain a drastic plasticity affecting numerous neurotransmission systems. In turn, the drug provokes a complex pattern of behavioral responses, including locomotor hyperactivity, stereotyped behaviors, sensitization, and appetitive and reinforcing properties that rapidly generate the addictive process. The involvement of sigma (1) receptors in cocaine effects has been suggested initially through the observation that sigma (1) antagonists could attenuate several acute effects induced by the drug, such as hyperlocomotion, stereotypies, convulsions and lethality. We will describe thereafter the recent results showing that activation of the sigma (1) receptor is also involved in the appetitive properties of cocaine, as measured using place preference conditioning in mice. Using selective sigma (1) antagonists or an in vivo antisense strategy, the role of the sigma (1) receptor in acquisition, expression and reactivation of conditioned place preference was demonstrated. The observation that repeated administration of cocaine rapidly provokes overexpression of the sigma (1) receptor outlines its major role in these first psychological steps of addictive processes. The physiological interaction between cocaine and sigma (1) receptors is detailed and the possibility that effective therapeutical strategies could target the sigma (1) receptor is considered.

Animals↗

PubMed1983

The molecular basis of a neuroendocrine fixed action pattern: egg laying in Aplysia.

We describe a gene family that encodes the proteins controlling the egg-laying behavior of Aplysia. The family evolved by duplication and divergence from a common ancestral gene. The ELH gene family is expressed in the atrial gland, in the bag cells, and in a small network of neurons in the central ganglia. The bag cells and the atrial gland express distinct members of the family that encode different precursor proteins. These contain one or more biologically active peptides that can be released by proteolytic cleavage. The bag cell precursor releases several peptides that have multiple sites of action and may generate different components of the egg-laying behavior. Coordination of the full stereotyped behavior is achieved by simultaneous release of these peptides from the bag cell processes.

Amino Acid Sequence↗

PubMed1988

A case of Tourette's syndrome with midbrain involvement.

Several hypotheses have attempted to incriminate a particular anatomical region responsible for the complex symptomatology of Tourette's syndrome (TS). Recently, Devinsky speculated that damage to the peri-aqueductal gray matter (PAG) and midbrain tegmentum may represent the major anatomical site of dysfunction in TS. A patient with TS in whom radiological evidence indicated midbrain involvement may support Devinsky's hypothesis. A 7-year-old boy exhibited motor and vocal tics since the age of four. These were associated with hyperactive behavior, stereotype body movements, abnormal sexual behavior and coprolalia. At the age of five he was placed on methylphenidate for hyperactive behavior which resulted in marked exacerbation of the tics. Family history was unremarkable. Neurological examination was normal with the exception of the tics. Endocrine evaluation, including plasma cortisol, growth hormone, prolactin and TSH were normal with the exception of reduced FSH, LH and testosterone levels. Sexual maturation was normal. MRI head scan was normal with the exception of an asymmetry of the cerebral peduncles with the left larger than the right. CSF examination was normal. While the nature of this patient's radiological abnormalities is not clear, our findings of asymmetric cerebral peduncles associated with TS may support a role for the midbrain in the pathophysiology of TS. The likelihood of the latter assumption seems to be further confirmed by a recent report in which peri-third ventricular and PAG calcifications were detected by CT scan of the head in an adult patient with TS. Further MRI investigations in other cases of TS may clarify the anatomical relationship of the midbrain to the symptomatology of TS.

Child↗

PubMed1989

[Maintenance and care of primates in Italy].

Investigation with nonhuman primates has made, and continues to make significant contribution to biomedical and behavioral research. Nowadays, laymen and scientists are becoming more concerned with the ways in which animals are maintained in captivity. In Italy, two laws (issued in 1931 and in 1941) enforce the regulations for keeping primates used for research. And more recently, the countries of the European Economic Community (EEC) have agreed on new regulations that should become law in these countries. Primates need to be in good physical and psychological health, and regulations should ensure and promote their well-being. Primates' psychological well-being is characterized by: a) good physical health; b) absence of stress; c) competence in dealing with environmental and social changes; d) broad behavioral repertoire and absence of stereotyped behaviors. Enrichment procedures aimed at improving the animals' psychological well-being are discussed.

Animal Husbandry↗

PubMed1996

Evidence for the involvement of phospholipase A2 mechanisms in the development of stimulant sensitization.

Evidence suggests that phospholipase A2 (PLA2) activation is involved in numerous neuroplastic phenomena, including long-term potentiation. Considering the pharmacological similarities between long-term potentiation and stimulant sensitization, it seems possible that PLA2 inhibition activity also might have a role in the induction of stimulant sensitization. In this study, we have investigated whether PLA2 inhibition, by quinacrine, has any effects on stimulant-induced behavioral sensitization. Both locomotor and stereotypic behavioral sensitization were dose-dependently blocked in rats pretreated with quinacrine (8-25 mg/kg i.p.) 15 min before cocaine (30 mg/kg i.p.), when tested with cocaine (15 mg/kg i.p) 72 hr later. Similar results also were found with d-amphetamine (2 mg/kg i.p.) sensitization using a 10-day treatment regimen with testing on day 11. The ability of PLA2 activation, by melittin, to produce cocaine sensitization also was tested. Local injections of melittin (0.1 microgram/0.4 microliter) into the ventral tegmental area sensitized the subsequent stimulation of locomotor activity, stereotypy and nucleus accumbens dopamine release by cocaine, when tested 72 hr later. Local injections of melittin (0.1-1.0 microgram/0.8 microliter) into the nucleus accumbens had a moderate sensitizing effect on locomotion. Quinacrine (16 mg/kg) pretreatment 45 min before intraventral tegmental area melittin injection significantly decreased melittin-induced sensitization of the locomotor and stereotypy response to cocaine. These results indicate that PLA2 activation may play a role in the induction of stimulant sensitization. It is proposed that PLA2 activity in mesolimbic dopamine neurons, at the level of the cell bodies and perhaps the nerve terminals, is involved in the biochemical mechanisms mediating the development of stimulant sensitization.

Animals↗

PubMed1999

Estrous cycle differences in cocaine-induced stereotypic and locomotor behaviors in Fischer rats.

This study was conducted to characterize female behavioral response to acute 'binge' pattern cocaine administration (15 mg kg(-1) i.p., three times a day, at 1 h intervals) during the different stages of the estrous cycle in Fischer rats. Cocaine administration significantly increased stereotypic behavior and locomotion in females. Animals in estrus showed significantly higher cocaine-induced stereotypic and locomotive behavioral responses than those in other stages of the cycle. Plasma levels of the cocaine metabolite benzoylecgonine during metestrus diestrus were significantly higher than during estrus and proestrus probably reflecting more rapid biotransformation of cocaine. Therefore, it is likely that the hormonal fluctuations associated with the estrous cycle modulate both cocaine metabolism and the behavioral responses to cocaine in female rats. This in turn may have important implications in gender differences in behavioral responses to cocaine.

Animals↗

PubMed1993

Naltrexone-induced pruritus in a dog with tail-chasing behavior.

Naltrexone, an opioid antagonist recently advocated for the control of stereotypic behavioral patterns in horses and dogs, induced an intense dose-related pruritic reaction in a dog with tail-chasing and self-mutilating behavior. Used in human beings primarily as an adjunct in the treatment of opioid abusers, naltrexone's adverse effects include dermatologic signs, such as alopecia and pruritus, observed in < 1% of human patients. In contrast to previously reported findings, naltrexone treatment was of limited benefit to the dog of this report. During administration of the drug, stereotypic patterns were reduced but did not disappear. Although naltrexone may be effective in controlling certain obsessive-compulsive disorders, its inconsistent therapeutic value, prohibitive cost to pet owners, and side effects such as the pruritus observed in the dog of this report may restrict use of this drug.

Animals↗

PubMed1991

The use of a brief movement restriction procedure to eliminate severe inappropriate behavior.

The effect of a brief movement restriction (BMR) procedure on the maladaptive behavior of two severely mentally retarded persons was evaluated using a multiple baseline research design. Following a functional analysis of the maladaptive behaviors, baseline data were collected on the frequency of smearing in a six year old boy and the frequency of aggression-destruction and stereotypic behavior in a 24 year old man. Following the baseline period a treatment package that included reinforcement for alternative behavior and BMR were first introduced for feces smearing. After feces smearing had shown a reduction with the first client the treatment package was introduced for aggression and destruction with the second client. After aggression and destruction had been reduced, the treatment package was added for stereotypy. The treatment package completely eliminated each of the target behaviors and they remained absent during a long follow-up period.

Adult↗

PubMed1984

Effect of age on behavioral responses and tissue levels of apomorphine in the rat.

Rats of several ages between 2 and 24 months were tested for stereotyped behavioral responses to R(-)apomorphine-HCl (APO), a potent and selective dopamine agonist. Between 2 and 24 months, the ED50 for apomorphine decreased 2.5-fold (0.14-0.06 mg/kg, i.p.), as assessed by a microcomputer-assisted technique. Not only were older rats more sensitive to apomorphine, but the duration of the behavioral effects increased with age and showed a greater change at doses which were greater than the ED50. When levels of apomorphine in brain were assayed by liquid chromatography and electrochemical detection, there was a progressive increase in peak levels of the agent in the tissue as well as a delay in its elimination from brain, with increasing age. Moreover, there was a highly significant correlation between increased behavioral effect and the level of apomorphine in brain with increasing age (r greater than 0.8). These results indicate that increased levels in brain or decreased elimination of apomorphine may be an important factor contributing to a marked increase in behavioral sensitivity to apomorphine with age in the rat.

Aging↗

PubMed1980

Evidence for the role of noradrenaline in some effects of quipazine.

In mice, quipazine has shown several behavioral effects: It antagonizes hypothermia induced by a high dose of apomorphine without altering climbing or stereotyped behavior; it antagonizes oxotremorine-induced hypothermia without altering tremors or peripheral signs; and it increases the toxicity of yohimbine. These three responses are considered to be predictive of an antidepressive action; in these three tests the effects of quipazine are inhibited by D,L-propranolol but not by D-propranolol or methysergide. Quipazine, in mice pretreated with pargyline, induced head twitches which were inhibited by methysergide but not by D,L-propranolol. Quipazine, in addition to its well-known serotonergic effects, seems to have beta-adrenergic properties which should be kept in mind when this drug is used as a pharmacological tool and which suggest that the beta-adrenergic system is implied in depression.

Animals↗

PubMed1976

Abolition of nomifensine-induced stereotypy after 6-hydroxydopamine lesions of ascending dopaminergic projections.

The effects of bilateral focal injections of 6-hydroxydopamine into the zona compacta of the substantia nigra (SNC) on nomifensine-induced stereotypy were examined in the rat. These lesions reduced neostriatal dopamine levels to less than 1 percent of control levels. They also abolished nomifensine-induced stereotyped behavior. It is suggested that nomifensine-induced stereotypy is mediated via a presynaptic action on dopamine uptake and release.

Animals↗

PubMed1982

Multiple postsynaptic dopamine receptors and behavioral manifestation.

Previously we demonstrated the existence of non- and positive-cooperative dopamine receptors in rat striatum in [3H] apomorphine binding experiments. Non-cooperative sites were sensitive to the inhibition of sulpiride while cooperative sites were not. In the present study results dealing with the involvement of those two types of postsynaptic dopamine receptors in different behavior manifestations is shown employing lisuride hydrogen maleate (LHM). LHM elicited contralateral turnings in 6-hydroxydopamine lesioned rats unilaterally in the striatum whereas it caused ipsilateral turnings in kainic acid lesioned rats as was observed following the administration of apomorphine. Furthermore, the effect of LHM on rotating behavior was abolished by the pretreatment with sulpiride. On the other hand, LHM inhibited apomorphine induced stereotyped behavior whereas the sulpiride failed to block it. These results suggested the dual action of LHM on multiple postsynaptic dopamine receptors. The results also indicated that non-cooperative postsynaptic dopamine receptors are involved in rotating behavior while cooperative receptors participate in the elicitation of stereotypy.

Animals↗

PubMed1999

Cortical damage enhances pemoline-induced self-injurious behavior in prepubertal rats.

Self-injurious behavior (SIB) is a devastating characteristic of several developmental disorders including a number of mental retardation syndromes. The functional neuroanatomy and neuropharmacology of SIB is not well understood. Self-biting behavior (SBB) can be induced in rats by a high dose, systemic injection of pemoline (250 mg/kg, SC). This animal model allows for the investigation of anatomical and pharmacological aspects of SIB. Cortical pathology is a common occurrence in human disorders with SIB, and may be a fundamental pathological factor in producing the behavior. The present experiment was designed to investigate the effects of cortical damage on pemoline-induced SBB in prepubertal rats. Bilateral cortical aspirations were performed in 3-5-week-old rats. One week postsurgery, a pemoline challenge was administered. Behavioral comparisons were completed between the lesion group and an anesthetized-only control group. Results indicated that cortical damage significantly enhanced pemoline-induced SBB, along with some of the other pemoline-induced stereotypical behaviors. These results support the hypothesis that cortical damage influences the expression of stimulant-induced self-injury, and potential mechanisms for this influence are suggested.

Animals↗

PubMed1985

Stimulation of dopamine D-1 receptors by SKF 38393 induces EEG desynchronization and behavioral arousal.

The dopamine D-1 receptor agonist SKF 38393 dose-dependently (2.5-10 mg/kg) induced desynchronization of the electroencephalographic (EEG) activity and behavioral arousal in both rabbits and rats. Unlike apomorphine, SKF 38393 elicited no signs of stereotyped behavior in rabbits and minimal effects, such as episodes of grooming, in rats. The effects of SKF 38393 10 mg/kg on the EEG were prevented by the selective D-1 receptor antagonist SCH 23390 at a dose as low as 0.003 mg/kg, but not by the D-2 antagonist (-)-sulpiride (25-50 mg/kg). These data provide evidence of a role of D-1 receptors in the generation of EEG activity related to behavioral arousal. In addition, this model is a valuable tool to functionally evaluate the D-1 antagonistic properties of neuroleptics.

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

PubMed1986

Repeated pemoline produces self-injurious behavior in adult and weanling rats.

Self-injurious behavior (SIB) is a serious problem among the mentally handicapped and is often accompanied by other repetitive or stereotyped behaviors. Acute administration of high doses of amphetamine or pemoline to rats produces transient SIB which is accompanied by severe deterioration of the behavioral repertoire. Repeated subcutaneous (SC) administration of pemoline to rats produces a high incidence of SIB without the dramatic behavioral changes produced by high doses of oral pemoline. Repeated pemoline increased locomotions and rears and produced intermittent stereotyped sniffing and licking/biting. However, the animals were still able to eat, drink, sleep and groom. Hotplate tests provided no evidence for analgesia. Because SIB is often associated with human developmental disorders, the effects of repeated SC administration of pemoline to weanling rats was also investigated. SC injections every 12 hours produced a high rate of SIB in weanling rats.

Animals↗