Retention of Spatial Delayed Alternation in Rats with Lesions in the Frontal Lobes

1993

Summary. The effects of systemic administration of dizocilpine (0.16 mg/kg, i.p.), clozapine (7.5 mg/kg, s.c.) and coadministration of dizocilpine (0.16rag/ kg, i.p.) and clozapine (7.5 mg/kg, s.c.) on acquisition of delayed alternation in a T-maze were tested in rats (N = 7 per group) on six days with 10 choices per day and animal. Clozapine given alone did not impair delayed alternation learnint, except of the first day. Dizocilpine induced a significant delayed alternation impairment on all days tested. Pretreatment with clozapine significantly improved the dizocilpine-induced impairment. Treatment-induced changes of delayed alternation learning and of locomotor activities showed no correlation. The results demonstrate that clozapine functionally compensated for deficits induced by a blockade of the N-methyl-D-asparatate (NMDA) subtype of glutamate receptors.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clozapine improves dizocilpine-induced delayed alternation impairment in rats

1993

“…This was in fact confirmed in different paradigms. For instance, lesions within the medial prefrontal cortex or the medial striatum produced similiar impairments in maze leafing (Dunnett and Iversen, 1981;Simon and LeMoal, 1984;Wikmark et al, 1973). The avaible catalepsy data further support a role of the motor loop for the expression of catalepsy: while extensive lesions of the frontal cortex reversed neuroleptic-induced catalepsy (Scatton et al, 1982;Warenycia etal., 1987;Worms etal., 1985;Yoshida etal., 1991), lesions of the medial prefrontal cortex induced only a weak anti-cataleptic effect (Carter and Pycock, 1987).…”

Section: Histologymentioning

confidence: 95%

“…On the other hand there is growing evidence that not only the anterio-posterior, but also the medio-lateral organization of the striatum is behaviourally relevant. Lesions in the medial part of the CP produced selective impairments in maze performance and discrimination learning (Wikmark et al, 1973;Divac et al, 1978;Pisa and Cyr, 1990;Hauber and Schmidt, 1989) whereas lesions in the lateral part of the CP induced motor deficits in various tasks (Sabol etal., 1985;Pisa, 1988;Pisa and Schranz, 1988;Pisa and Cyr, 1990). The medial and lateral subregion of the CP mediate behavioural functions which are related to those mediated by the anatomically linked regions of the cortex.…”

Section: Introductionmentioning

confidence: 99%

Discrete quinolinic acid lesions of the lateral but not of the medial caudate-putamen reversed haloperidol-induced catalepsy in rats

Schmidt

1993

Summary. Discrete lesions in the medial or lateral subregion of the rostral caudate-putamen (CP) were induced by bilateral intracerebral injections of a low dose of quinolinic acid (30 nmol in 1 gl/per side) in rats. Quinolinic acid lesions in the lateral CP potently reversed haloperidol-induced catalepsy (0.5 mg/ kg,i.p.), while lesions in the medial CP were not effective. Spontaneous locomotor activity was not altered significantly after quinolinic acid lesions of either the medial or lateral CP. These results show that the lateral CP seems to be important for the expression of neuroleptic-induced catalepsy and thus further corroborate the concept of a functional heterogenity of the striatum.

“…The adequate and sensitive paradigm for rodents is a delayed alternation task in the T-or Y-maze. Mechanical or neurotoxic lesions in the antero-dorsal striatum of rats produce severe impairments in delayed alternation tasks and increase alternation to chance level (Pisa, 1983;Wikmark et al, 1973). In addition, amphetamine also induces a spatial alternation deficiency that is characterized by perseverative tendencies and alternation below chance level.…”

Section: Introductionmentioning

confidence: 99%

Effects of intrastriatal blockade of glutamatergic transmission on the acquisition of T-maze and radial maze tasks

Schmidt

1989

Summary. Prefrontal cortex and neostriatum constituting the prefrontal system are connected by glutamatergic neurones. The involvement of this corticostriatal projection in control of maze performance of rats was investigated. Glutamatergic transmission mediated by N-methyl-D-aspartate (NMDA) receptors was blocked by intrastriatal injections of dl-2-amino-5-phosphonovaleric acid (AP-5) (50 nmole in 0.5 ILl). In experiment 1, intrastriatal AP-5 was found to increase the number of errors during acquisition of a delayed alternation task in a T-maze. In experiment 2, the effect of intrastriatal AP-5 on acquisition of different 8 arm maze tasks was investigated. AP-5 did not affect the number of reentries on spontaneous and reinforced alternation; pre-and postdelay errors on delayed alternation were not altered. Therefore, intrastriatal NMDA receptor blockade impairs acquisition of a delayed alternation in a Tmaze, while intrastriatal blockade of NMDA receptors does not affect acquisition of different 8 arm maze tasks. The impairment in the T-maze task appears not to be due to deficient acquisition of spatial information per se, since 8 arm maze performance is intact. Instead, repeated delays in the T-maze task seem to be the critical component that gives difficulties in acquisition. These difficulties in bridging successive temporal discontiguities were attributed to an increased susceptibility to external and internal interfering stimuli during delays. Thus, striatal NMDA receptors within the prefrontal system may be involved in correct response retention over the duration of delays.