An observational method for quantifying the behavioural effects of dopamine agonists: Contrasting effects of d-Amphetamine and apomorphine

Fray, P.J.; Sahakian, Barbara J.; Robbins, Trevor W.; Koob, George F.; Iversen, Susan D.

doi:10.1007/bf00433091

Cited by 333 publications

(117 citation statements)

References 22 publications

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“…or s.c.), followed 45 min later by s.c. injection of apomorphine (2.5 mg/kg). The observational method used was an adaptation of the method of Fray et al (1980), combined with a time-sampling procedure (Waddington, 1986).…”

Section: Apomorphine-induced Climbing and Sniffingmentioning

confidence: 99%

Antipsychotic-Like vs Cataleptogenic Actions in Mice of Novel Antipsychotics Having D2 Antagonist and 5-HT1A Agonist Properties

Bardin

Kleven

Barret-Grévoz

et al. 2005

Neuropsychopharmacol

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A new generation of proven or potential antipsychotics, including aripiprazole, bifeprunox, SSR181507 and SLV313, exhibit agonist actions at serotonin 5-HT 1A receptors, but little comparative data are available on their pharmacological profiles. Here, we compared in mice the in vivo antipsychotic-like vs cataleptogenic activities of these compounds with those of drugs that exhibit little interaction at 5-HT 1A receptors, such as haloperidol, olanzapine and risperidone. All the drugs dose-dependently reduced apomorphine-induced climbing or sniffing and, with the exception of ziprasidone, produced complete suppression of these responses. In the bar catalepsy test, when administered alone, haloperidol, olanzapine and risperidone produced marked catalepsy, whereas, at doses up to 40 mg/kg, aripiprazole, SLV313, SSR181507, and sarizotan produced little or no catalepsy. The latter compounds, therefore, displayed a large separation between doses with 'antipsychotic-like' and those with cataleptogenic actions. When 5-HT 1A receptors were blocked by pretreatment with WAY100635 (2.5 mg/kg, s.c.), cataleptogenic properties of SSR181507 and sarizotan were unmasked, and the catalepsy induced by bifeprunox was enhanced. In the case of aripiprazole and SLV313, although WAY100635 produced upward shifts in their dose-response, the magnitude of catalepsy appeared to reach an asymptotic plateau, suggesting that other mechanisms may be involved in their low cataleptogenic liability. The present data confirm that 5-HT 1A receptor activation reduces or even completely prevents the cataleptogenic potential of novel antipsychotic agents. Further, they indicate that the balance of affinity and/or efficacy between D 2 and 5-HT 1A receptors profoundly influences their pharmacological activities, and will likely impact their therapeutic profiles.

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Section: Apomorphine-induced Climbing and Sniffingmentioning

confidence: 99%

Antipsychotic-Like vs Cataleptogenic Actions in Mice of Novel Antipsychotics Having D2 Antagonist and 5-HT1A Agonist Properties

Bardin

Kleven

Barret-Grévoz

et al. 2005

Neuropsychopharmacol

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“…Different drugs result in stereotypies that differ in typical appearance (reviewed by Robbins & Sahakian 1981), response to a dose increase (Fray et al 1980), and the way in which they are affected by, for example, fooddeprivation (see e.g. MacLennan & Maier 1983).…”

Section: Stimulant-induced and En Vironment-induced Stereotypiesmentioning

confidence: 99%

Stereotypies: a critical review

1991

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Abstract. Stereotypies are repetitive, invariant behaviour patterns with no obvious goal or function. They seem to be restricted to captive animals, mentally ill or handicapped humans, and subjects given stimulant drugs. In this respect they are abnormal, although possibly the product of normal behavioural processes. Stereotypies are often associated with past or present sub-optimal aspects of the environment, and have been used as a welfare indicator. It has been hypothesized that stereotypies have beneficial consequences which reinforce their performance, although other means, such as positive feedback, may equally explain their persistence. Empirical evidence links them with lowered awareness of external events, and reduced arousal and distress. However, as most of this evidence is correlational it remains uncertain that the stereotypies are themselves the cause of coping. Furthermore, they are heterogeneous in source of origin, proximate causation and physical characteristics, and they change over time in important respects, becoming more readily elicited by a wider range of circumstances. Therefore the properties of one stereotypy are not necessarily those of another.

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“…Observers, who were unaware whether rats were characterized as LCRs or HCRs, scored behavior in 60-s intervals for the 30 min before and 1 h after injection using the following categories: 'nonmovement,' defined as inactivity or sleeping; 'grooming,' defined as movements directed against self that typically include forepaw movements over the body, scratching, licking, body gnawing, and face washing; 'head movement/sniffing,' defined as movements of the head and/ or sniffing that occurred in the presence of discrete upper or lower body movements but in the absence of locomotion; 'exploring,' defined as locomotion around the activity chamber that was continuous or occurred in repeated bouts and typically includes head movements and sniffing; 'stereotypy,' defined as repetitive head movements and sniffing, head bobs, and/or side-to-side head sways that were directed at the environment and were confined to a small area of the chamber; and 'rearing,' defined as the lifting of both forepaws off the floor with posture maintained on the hind legs. With the exception of rearing, behaviors were scored on a binary scale (0 ¼ absent; 1 ¼ present), with those expressed for at least 10 consecutive seconds of a 60-s interval scored as present (Fray et al, 1980;Sabeti et al, 2002). In cases where no single behavior persisted for 10 s, the behavior expressed during the majority of the 60-s interval was considered present.…”

Section: Initial Behavioral Characterizationmentioning

confidence: 99%

Individual Differences in Cocaine-induced Locomotor Activity in Rats: Behavioral Characteristics, Cocaine Pharmacokinetics, and the Dopamine Transporter

Gulley

Hoover

Larson

et al. 2003

Neuropsychopharmacol

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Outbred male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on their locomotor response to acute cocaine. Concomitant measurement of dopamine clearance in these rats revealed that the differential behavioral responses are associated with the magnitude of dopamine transporter (DAT) inhibition by cocaine. Here, we investigated several factors that might contribute to cocaine-induced behavioral variability and its association with differential inhibition of DAT function. In rats classified as LCRs or HCRs after 10 mg/kg cocaine injection, we found no differences in (1) novelty-induced locomotion, (2) cocaine levels in dorsal striatum or nucleus accumbens (NAc), (3) DAT number or affinity in NAc, or (4) DAT affinity for cocaine in NAc. In rats given 20 mg/kg cocaine, behavior was more uniform across individuals, but still warranted separation into LCR/HCR categories. Additionally, we analyzed the stability of the LCR/HCR classification made during the first test with 10 or 20 mg/kg cocaine by retesting rats 7 days later with saline or cocaine (10 or 20 mg/kg). Before injection, HCRs were more active relative to LCRs and to their own behavior on the first test day. Following cocaine, LCRs and HCRs exhibited similar drug-induced changes in locomotion, but there were unique effects that depended on the cocaine dose given on the first and second test days. Our results argue against several likely explanations for individual differences in cocaine-induced behavior and highlight the influence of a single cocaine exposure on subsequent behavioral responses to the drug.

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An observational method for quantifying the behavioural effects of dopamine agonists: Contrasting effects of d-Amphetamine and apomorphine

Cited by 333 publications

References 22 publications

Antipsychotic-Like vs Cataleptogenic Actions in Mice of Novel Antipsychotics Having D2 Antagonist and 5-HT1A Agonist Properties

Antipsychotic-Like vs Cataleptogenic Actions in Mice of Novel Antipsychotics Having D2 Antagonist and 5-HT1A Agonist Properties

Stereotypies: a critical review

Individual Differences in Cocaine-induced Locomotor Activity in Rats: Behavioral Characteristics, Cocaine Pharmacokinetics, and the Dopamine Transporter

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