title: Quinpirole and 8-OH-DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit.
abstract: This study investigated whether the serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) can induce compulsive checking in a large open field, as does the dopamine D2/D3 receptor agonist quinpirole. To induce compulsive checking, male rats were exposed to eight injections of either 8-OH-DPAT (1 mg/kg), quinpirole (0.2 mg/kg), or saline. Subsequently, to assess cross-sensitization, rats received an acute challenge of 8-OH-DPAT or quinpirole. The results showed that treatment with 8-OH-DPAT induces compulsive checking and may have a stronger effect on this behavior compared with quinpirole. However, there was no cross-sensitization between 8-OH-DPAT and quinpirole on measures of compulsive checking and locomotion. Moreover, the spatial distribution of locomotor paths in 8-OH-DPAT animals was more confined and invariant than in quinpirole rats; their rate of locomotor sensitization was also faster than that in quinpirole animals. Thus, although 8-OH-DPAT and quinpirole can induce compulsive checking in a large open field, the results suggest that they do so differently. It is suggested that 8-OH-DPAT and quinpirole probably produce compulsive behavior by acting on different parts of a security motivation circuit underlying obsessive-compulsive disorder. Quinpirole may induce compulsive checking behavior by directly driving dopaminergic activity mediating the motivational drive to check. Conversely, 8-OH-DPAT may perpetuate the activated motivational state by inhibiting the serotonergic-negative feedback signals that normally deactivate the obsessive-compulsive disorder circuit.
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Ahmad H
authors.initials: AH
authors.lastname: Alkhatib
authors.forename: Anna
authors.initials: A
authors.lastname: Dvorkin-Gheva
authors.forename: Henry
authors.initials: H
authors.lastname: Szechtman
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003192:Compulsive Behavior / Q000139:chemically induced; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D009419:Nerve Tissue Proteins / Q000819:agonists*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced*; D019257:Quinpirole / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists / Q000633:toxicity; D058826:Serotonin 5-HT2 Receptor Agonists / Q000633:toxicity; D058827:Serotonin 5-HT3 Receptor Agonists / Q000633:toxicity; D017366:Serotonin Receptor Agonists / Q000633:toxicity*; D013037:Spatial Behavior / Q000187:drug effects
chemical_list: D009419:Nerve Tissue Proteins; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058827:Serotonin 5-HT3 Receptor Agonists; D017366:Serotonin Receptor Agonists; D019257:Quinpirole; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin