title: The 5-HT2 receptor agonist MK-212 reduces food intake and increases resting but prevents the behavioural satiety sequence.
abstract: The 5-HT2c receptor is implicated in the relationship between serotonin and satiety. However, anorexia induced by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) has been shown to delay, not advance behaviours associated with the onset of satiety, fragmenting eating behaviour, 6-chloro-2-(1-piperazinyl)pryazine (MK-212) is also a selective agonist at the 5-HT2 receptor sites. MK-212 has greater affinity for 5-HT2c receptor sites than DOI. The effects of an ED50 dose of MK-212 (5.0 mg/kg i.p.) on the eating and other behaviours of the fasted rat were continuously monitored following the presentation of food. Continuous monitoring provides the most powerful and valid form of behavioural analysis. Temporal profiles of behaviour duration (dur) and frequency (frq) were generated. Food intake was reduced 54% by MK-212 (p < .001). The frequency of grooming was reduced (p < .01). Locomotion (dur p < .001, frq p < .001), rearing (dur p < .0005, frq p < .005) and sniffing (dur p < .05, frq p < .0001) were all reduced. The duration of resting increased (p < 0.01). This is consistent with enhanced satiety. However, the Behavioural Satiety Sequence was not present after the administration of MK-212 (5.0 mg/kg). The temporal structure of behaviour produced by MK-212 was quite different from that produced by pre-feeding. Initially resting dominated the behavioural profile. Eating increased over time from a suppressed state in the initial stages of the observation period. This lack of appearance of the Behavioural Satiety Sequence is more similar to a state of hyper-sedation than to DOI induced hyper-activity. The time course of this sedation would not have been picked up by a simple categorical analysis of behaviour. Hence, temporal analysis is an essential tool in understanding of drug induced anorexia.
authors.affiliation: BioPsychology Group, University of Leeds, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Halford
authors.forename: C L
authors.initials: CL
authors.lastname: Lawton
authors.forename: J E
authors.initials: JE
authors.lastname: Blundell
mesh_terms: D000818:Animals; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D006120:Grooming / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D012528:Satiety Response / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D011719:Pyrazines; D017366:Serotonin Receptor Agonists; C014896:6-chloro-2-(1-piperazinyl)pyrazine