D1 and D2 dopamine receptor antagonists decrease behavioral bout duration, without altering the bout's repeated behavioral components, in a naturalistic model of repetitive and compulsive behavior.
Nest building behavior in the pregnant female rabbit (Oryctolagus cuniculus) is a model for compulsive behavior in Obsessive Compulsive Disorder (OCD). This behavior comprises a cycle of repeated, stereotyped components (collecting straw, entering nest box and depositing the straw there, returning to collect more straw), which itself is repeated 80+ times in a single bout that lasts approximately 50min. The bout, in turn, is repeated if necessary, according to the rabbit's perception of whether or not the nest is finished. We administered SCH23390 (5-100μg/kg; D1/D5 antagonist) or raclopride (0.05-1.0mg/kg; D2/D3 antagonist), subcutaneously to day 28 pregnant female rabbits, 30 or 60min before placing straw inside their home cage. At doses that minimally affected ambulatory behavior in open field (5-12.5μg/kg SCH23390, 0.5-1.0mg/kg raclopride), both antagonists dramatically reduced bout duration while not significantly affecting the initiation of straw carrying behavior, the sequential performance of the individual cycle components, maximum cycle frequency, or the total number of bouts performed. These results point to an important role for dopamine neurotransmission for the prolonged expression of a normal, repetitive and compulsive-like behavior. Moreover, the finding that dopamine receptor antagonists decrease the time spent engaged in repetitive behavior (without significantly altering the form of the repetitive behavior itself) suggests a possible explanation for why neuroleptics can be clinically effective for treating OCD.
Centro de Investigación en Reproducción Animal (CIRA), CINVESTAV-Universidad Autónoma de Tlaxcala, 90000 Tlaxcala, Mexico. rexvitro@hotmail.com
Kurt L
KL
Hoffman
Rafael I
RI
Rueda Morales
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000627:therapeutic use*; D003192:Compulsive Behavior / Q000188:drug therapy*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008425:Maternal Behavior / Q000187:drug effects* / Q000502:physiology; D009425:Nesting Behavior / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011817:Rabbits; D020891:Raclopride / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; C534628:SCH 23390; D020891:Raclopride