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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 21 (2005), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The use of reward-predictive cues to guide behavior critically involves the nucleus accumbens. However, little is known regarding the role of ionotropic glutamate receptors in the core subregion of the nucleus accumbens (AcbC) in instrumental learning guided by reward-predictive cues. Here we examined the effects of an intra-AcbC blockade of NMDA and AMPA/KA receptors on the acquisition of an instrumental response in a reaction time (RT) task in rats. In this task, discriminative cues signaled in advance the upcoming reward magnitude (5 or 1 food pellet) associated with a lever release. During early acquisition (days 1–6) rats received daily bilateral injections of either the NMDA receptor antagonist AP5 (5.0 µg per side, n = 14), the AMPA/KA receptor antagonist CNQX (2.5 µg per side, n = 14) or vehicle (0.5 µL per side, n = 19). No treatment was given during late acquisition (days 7–12). The main result was that rats which received intra-AcbC injections of AP5 or CNQX during early acquisition exhibited a general RT increase of responses to high and low reward. However, treatment with AP5 and CNQX did not interfere with discriminative guidance of RTs by cue-associated reward magnitudes, i.e. during acquisition RTs of responses to expected high reward became significantly faster than RTs of responses to expected low reward. Our findings suggest that NMDA and AMPA/KA receptors in the AcbC play a critical role in invigorating responding during instrumental learning, but seem less important in guiding responding according to reward-predictive cues.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 18 (2003), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The present study examined the involvement of N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolpropionate/kainate (AMPA/KA) and dopamine receptors in the nucleus accumbens (ACB) in influencing reaction times of instrumental responses by the expectancy of reward. A simple reaction time task demanding conditioned lever release was used in which the upcoming reward magnitude was signalled in advance by discriminative cues. After training, in control rats with vehicle infusions (0.5 µL) into the ACB, reaction times of responses were significantly shorter to the discriminative cue predictive of high reward magnitude. Indirect stimulation of dopamine receptors in the ACB by d-amphetamine (20 µg/0.5 µL) decreased reaction times, impaired their guidance by cue-associated reward magnitudes and reduced the accuracy of task performance. Blockade of AMPA/KA receptors in the ACB by 6-cyano-7-nitroquino-xaline-2,3-dione (0.75 and 2.5 µg/0.5 µL) or NMDA receptors by d(−)-2-amino-5-phosphonopentanoic acid (5 µg/0.5 µL) produced a general increase in reaction times, but left guidance of reaction times by cue-associated reward magnitudes unaffected. Thus, stimulation of intra-ACB ionotropic glutamate receptors is critically involved in modulating the speed of instrumental responding to cues predictive for reward magnitude, but is not required for intact performance of previously learned instrumental behaviour.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The present study sought to determine, in more detail, the effects of an unselective and a selective adenosine A2A receptor blockade on catalepsy induced by a blockade of dopamine D1 or D2 receptors in rats. The results demonstrated that systemic administration of the unselective A1/A2 receptor antagonist, theophylline and the selective A2A receptor antagonist, CSC potently reversed catalepsy induced by a systemic D2 receptor blockade with raclopride or by a bilateral blockade of D2 receptors in the caudate-putamen (CPu) with S(–)sulpiride. Likewise, systemic administration of theophylline and CSC reversed catalepsy induced by a systemic D1 receptor blockade with SCH23390; theophylline also counteracted catalepsy after an intra-CPu D1 receptor blockade with SCH23390. Intracerebral co-microinfusions of the selective A2A receptor antagonist, MSX-3 together with a D1 (SCH23390) or D2 receptor [S(–) sulpiride] antagonist revealed that catalepsy due to intra-CPu D1 or D2 receptor blockade can be potently reversed by an intra-CPu A2A receptor blockade. In conclusion, our results with systemic and intra-CPu drug administration demonstrate that D1 and D2 receptor-mediated catalepsy can both be reversed by a concomitant blockade of A2A receptors. Our results implicate that the CPu is a critical neural substrate for antagonistic interactions of a D1/D2 receptor blockade and an A2A receptor blockade in control of motor activity. The present results provide further support for the view that A2A receptor antagonists may be potential therapeutics for the treatment of Parkinson's disease.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1912
    Keywords: NMDA receptors ; Non-NMDA receptors ; Dizocilpine ; GYKI 52466 ; Locomotion ; Haloperidol-induced catalepsy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of the non-NMDA glutamate receptor antagonist GYKI 52466 (2.4 and 4.8 mg/kg, i.p.) on spontaneous locomotor activity and haloperidol-induced catalepsy (0.5 mg/kg, i.p.) were assessed in naive rats and in rats pretreated with the NMDA antagonist dizocilpine (0.08 mg/kg, i.p.). GYKI 52466 given alone did not alter locomotor activity and haloperidol-induced catalepsy, but significantly antagonized the dizocilpine-induced locomotor stimulation and counteracted the anti-cataleptic effects of dizocilpine on haloperidol-induced catalepsy. Thus blockade of non-NMDA glutamate receptors antagonized the behavioural stimulant effects of a NMDA receptor blockade.
    Type of Medium: Electronic Resource
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