The Effect Of Stereo Tactic Limbic Leucotomy Lesion On Compulsive Checking Behavior And Dopamine In Rats

THE FIRST PART Establishment and value an animal model of obsessive-compulsive disorderObjective: obsessive-compulsive disorder (OCD) is acomplexity, intractable, easy recrudesce, psychiatric disordercharacterized by recurring obsessions or compulsions. For manyyears, OCD was seen as infrequency and resist therapy. Newepidemiologic studies demonstrate that 2%-3% of the adultpopulation has OCD. There is strong evidence thatneurobiologic as well as psychologic and heritability factorsplay an important role in the pathogenesis of OCD, but thereliable mechanism remains unknown. We expect to establishOCD rats animal model, and provide theory evidence for newmethods to treat OCD.Methods: Health male SD rats which weigh were rangingfrom 250 to 300 grams were randomly divided into 3 groups. (1)Saline control group; (2) QNP group; (3) QNP andClomipramine group. Rats were treated chronically withdopamine D2/D3 agonist quinpirole (QNP) (0.5mg/Kg, twiceweekly x10). We observed the change of rats'behaviors in alarge mirror glass open-field on recorder after injection. 6indexes about behavior were observed: return frequency toprefer location, average duration of return home, visit sites, totaldistance of travel, sequence of visit, ratio of observed toexpected returns to the home case. We validated some criteriafor performance of compulsive checking.Results: Rats were induced pronounced compulsivebehavior on the open-field after 10 injections. The times thatreturned to the home case was nine times to saline group. Ratstraveled total distance was 380.7±106.8, distributing to 19.45±3.08 sites throughout the test. The ratio of observed toexpected was almost 5 times, that evidently more than salinegroup rats;The average duration of return home is about 1/9 ofsaline group. QNP group stopped only 2 sites compared 8 sitesto saline group when they visited continually one prefer object.Saline group rats had less locomotion throughout test.Clomipramine could partly attenuate compulsive checking. Thefrequency of return, the speed of return home, total distance ofClomipramine group are less than QNP group(p<0.05). All ofthis indicated Clomipramine partly attenuated compulsivechecking.Conclusions: QNP is a psychic motor stimulation, couldinduce notability locomotion sensitization after chronicallymanagement. Compulsive checking of rats has face resemblancewith clinic OCD, met DA theory of OCD pathogenesis. Thecompulsive checking induced by QNP was relativelyinvariableness, reputably. QNP rats were seen as an animalmodel of OCD and be used in clinic investigation.THE SECOND PART The effect of stereo tactic limbic leucotomy lesion on obsessive-compulsive disorder in ratsObjective: We used drugs and physic methods et al to treatOCD in clinic. But some patients had not effect, so theirdiseases developed deformity. These patients would beconsidered to operate. Neurosurgery had difference effectiveabout 40%-70%, some patients even could recrudesce aftersurgery. So we need discuss the mechanism of surgery toimprove curative effect and to ameliorate fashion of operation.We explored the effect of limbic leucotomy by using stereotactic technique on compulsive checking in QNP rats. We expectto offer theoretic evidence.Methods: we used QNP to establish OCD animal model.Then we managed with the stereo tactic limbic leucotomy lesion(the anterior cingulated and caudate were lesion), we observedbehavior index and compared the change of locomotion withClomipramine bundle.Results: The compulsive checking of rats after limbicleucotomy were attenuated, Indexes of return frequency to home,average duration of return home, total distance of travel,sequence of visit, ratio of observed to expected returns to thehome all had significantly differentiation compared withpseudo-lesion bundle (p<0.05). Compared with Clomipraminebundle some indexes had differentiation. The effect of behaviorchange after Clompramine treatment assembled with surgerybundle(p>0.05). The compulsive checking behavior afterClompramine treatment had obviously improving comparingwith QNP group (p<0.05).Conclusions: Limbic leucotomy can improve compulsivechecking in rats. So it can cure OCD, the effect analogy withdrug.THE THIRD PART The effect of dopamine after stereotactic limbic leucotomy lesion on ratsObjective: The turbulence of 5-hysroxytryptamine systemand Catecholamine system relate OCD, DA receptor distributemainly in CSTC loop, connect with limbic system. To exploreDA content in central dopaminergic terminal regions of OCDrats that could help us understand the pathology and biology ofOCD. All of this could provide evidence of psychosurgery torefractory OCD and guide us to investigate new drug.Methods: All rats were decapitated after two weeks oflimbic leucotomy, dopaminergic terminal regions were rapidlydissected on ice and frozen. Left and right prefrontal cortex(PFC), caudate/putamen (striatum), nucleus accumbens andamygdale were dissected according rat brain anatomic atlas. Allspecimens were stored at -80℃for subsequent analysis DAcontent by high performance liquid chromatography (HPLC)electrochemical detection.Results: DA content in prefrontal cortex(medial cortex andcingulated) was measured after chronic treat QNP. Left PFC was...