PMC:3813744 / 33589-36493 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3813744","sourcedb":"PMC","sourceid":"3813744","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3813744","text":"Acute 5-HT2CR Antagonism and Egocentric Reversal Learning\nAcute 5-HT2CR antagonism by SB242084 facilitated the ability to overcome perseverance, observed as a decrease in trials and incorrect responses to criterion. SB242084 also caused a concurrent impairment in the ability to overcome learned non-reward by increasing the number of trials to criterion. These opposing effects appear to have summated in the full reversal task, leading to no overall effect. It is very likely that these effects reflect 5-HT2CR blockade, rather than effects on another receptor mechanism. SB242084, especially at the relatively low dose used here, is highly selective for the 5-HT2CR, acting as a full antagonist or inverse agonist [34].\nThe observed effect of SB242084 in the perseverance test is in agreement with previous studies indicating that acute 5-HT2CR antagonism attenuates perseverative responding [15], [30]. It has been suggested that the SB242084-induced facilitation of operant lever reversal learning in the rat is related to decreased perseverance, as systemic or OFC-specific infusions of SB242084 can decrease repetitive responding towards the previous CS+ [30] or incorrect responses made early in reversal when responding is biased towards the previous CS+ [15]. In the learned non-reward test SB242084 impaired performance, seen as an increase in trials to criterion, in contrast to the effect seen in the perseverance test. This effect differs from the facilitating effects of SB242084 on learned non-reward in an instrumental analogue of the current protocol [16], indicating that egocentric and visuospatial reversal learning may involve different neural mechanisms.\nAlthough little is known about the pharmacology of learned non-reward, work has been done in the closely related paradigm of latent inhibition, which like learned non-reward, could be thought of as the persistence of non-reinforced associations. In this paradigm, SSRIs and atypical antipsychotics can both elevate and attenuate latent inhibition depending on the number of pre-exposures and strength of the non-reinforced association [35], [36]. Interestingly, these two classes of compound do have 5-HT2CR antagonism as a common pharmacological property in addition to their other quite disparate effects [37], [38].\nThe effects of 5-HT2CR antagonism on visuospatial reversal learning have previously been discussed in relation to altered 5-HT and dopamine signalling [15], [39]. The 5-HT2CR receptor tonically inhibits dopamine (and noradrenaline) signalling in the PFC [40] and dorsal [32] and ventral striatum [41], However, this same group of studies show that the effects of 5-HT2CR antagonists on tonic serotonin signalling is much less evident. The implication may be that it is phasic release of serotonin that is responsible for the effects of these antagonists in the behavioural context of reversal learning [42].","divisions":[{"label":"Title","span":{"begin":0,"end":57}}],"tracks":[{"project":"2_test","denotations":[{"id":"24204954-9225286-87518378","span":{"begin":718,"end":720},"obj":"9225286"},{"id":"24204954-20089901-87518379","span":{"begin":902,"end":904},"obj":"20089901"},{"id":"24204954-20089901-87518380","span":{"begin":1163,"end":1165},"obj":"20089901"},{"id":"24204954-22644128-87518381","span":{"begin":1570,"end":1572},"obj":"22644128"},{"id":"24204954-9050900-87518382","span":{"begin":2286,"end":2288},"obj":"9050900"},{"id":"24204954-8876023-87518383","span":{"begin":2292,"end":2294},"obj":"8876023"},{"id":"24204954-21353665-87518384","span":{"begin":2455,"end":2457},"obj":"21353665"},{"id":"24204954-9776391-87518385","span":{"begin":2552,"end":2554},"obj":"9776391"},{"id":"24204954-19553455-87518386","span":{"begin":2568,"end":2570},"obj":"19553455"},{"id":"24204954-10579808-87518387","span":{"begin":2594,"end":2596},"obj":"10579808"},{"id":"24204954-17996955-87518388","span":{"begin":2900,"end":2902},"obj":"17996955"},{"id":"T40931","span":{"begin":718,"end":720},"obj":"9225286"},{"id":"T47264","span":{"begin":902,"end":904},"obj":"20089901"},{"id":"T4615","span":{"begin":1163,"end":1165},"obj":"20089901"},{"id":"T61097","span":{"begin":1570,"end":1572},"obj":"22644128"},{"id":"T94738","span":{"begin":2286,"end":2288},"obj":"9050900"},{"id":"T22946","span":{"begin":2292,"end":2294},"obj":"8876023"},{"id":"T19865","span":{"begin":2455,"end":2457},"obj":"21353665"},{"id":"T97054","span":{"begin":2552,"end":2554},"obj":"9776391"},{"id":"T86810","span":{"begin":2568,"end":2570},"obj":"19553455"},{"id":"T97309","span":{"begin":2594,"end":2596},"obj":"10579808"},{"id":"T603","span":{"begin":2900,"end":2902},"obj":"17996955"}],"attributes":[{"subj":"24204954-9225286-87518378","pred":"source","obj":"2_test"},{"subj":"24204954-20089901-87518379","pred":"source","obj":"2_test"},{"subj":"24204954-20089901-87518380","pred":"source","obj":"2_test"},{"subj":"24204954-22644128-87518381","pred":"source","obj":"2_test"},{"subj":"24204954-9050900-87518382","pred":"source","obj":"2_test"},{"subj":"24204954-8876023-87518383","pred":"source","obj":"2_test"},{"subj":"24204954-21353665-87518384","pred":"source","obj":"2_test"},{"subj":"24204954-9776391-87518385","pred":"source","obj":"2_test"},{"subj":"24204954-19553455-87518386","pred":"source","obj":"2_test"},{"subj":"24204954-10579808-87518387","pred":"source","obj":"2_test"},{"subj":"24204954-17996955-87518388","pred":"source","obj":"2_test"},{"subj":"T40931","pred":"source","obj":"2_test"},{"subj":"T47264","pred":"source","obj":"2_test"},{"subj":"T4615","pred":"source","obj":"2_test"},{"subj":"T61097","pred":"source","obj":"2_test"},{"subj":"T94738","pred":"source","obj":"2_test"},{"subj":"T22946","pred":"source","obj":"2_test"},{"subj":"T19865","pred":"source","obj":"2_test"},{"subj":"T97054","pred":"source","obj":"2_test"},{"subj":"T86810","pred":"source","obj":"2_test"},{"subj":"T97309","pred":"source","obj":"2_test"},{"subj":"T603","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec9397","default":true}]}]}}