Effects of local application of dopaminergic drugs into the dorsal part of the medial prefrontal cortex of rats in a delayed matching to position task: comparison with local cholinergic blockade

Broersen, Laus M.; Heinsbroek, Rob P.W.; Bruin, Jan; Joosten, R; Hest, Annemieke van; Olivier, Berend

doi:10.1016/0006-8993(94)91644-6

Cited by 46 publications

(16 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A subsequent study employing an operant version of a delayed matching-toposition paradigm confirmed that DA receptors in the PFC also mediate working memory performance in well-trained rats. Specifically, microinfusion of either the nonselective DA antagonist flupentixol or the D 1 antagonist SCH 23390 produced what was termed "delay-independent" impairments in performance when delays between sample and response phases ranged from 1.5 to 30 s (Broersen et al 1995). However, these effects were also accompanied by an increase in response latencies, interpreted to mean that the effects of DA receptor blockade were due to a general disruption in performance that could not "be attributed to a specific impairment in short-term memory."…”

Section: Working Memorymentioning

confidence: 99%

Mesocortical dopamine modulation of executive functions: beyond working memory

2006

View full text Add to dashboard Cite

Whereas PFC D1 receptor activity is of primary importance in working memory, D1 and D2 receptors act in a cooperative manner to facilitate behavioral flexibility. We note that the principle of the "inverted U-shaped" function of D1 receptor activity mediating working memory does not necessarily apply to other PFC functions. DA in different subregions of the PFC also mediates decision-making assessed with delay discounting or effort-based procedures, and we report that D1, D2, and D4 receptors in the medial PFC contribute to decision-making when animals must bias the direction of behavior to avoid aversive stimuli, assessed with a conditioned punishment procedure. Thus, mesocortical DA modulation of distinct executive functions is subserved by dissociable profiles of DA receptor activity in the PFC.

show abstract

Section: Working Memorymentioning

confidence: 99%

Mesocortical dopamine modulation of executive functions: beyond working memory

2006

View full text Add to dashboard Cite

show abstract

“…In the rat, T-mazedelayed alternation (Simon et al, 1980;Brito et al, 1982;Stam et al, 1989;De Brabander et al, 1991) as well as operant delayedmatching-to-position (Dunnett, 1985;Broersen et al, 1994), are routinely used to assess this function. Previous studies from our laboratory have reported that subanesthetic doses of ketamine impair the performance of rats in a T-maze-delayed alternation paradigm (Verma and Moghaddam, 1996).…”

Section: Mechanism By Which Ketamine Increases Dopamine Release In Thmentioning

confidence: 99%

Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex

et al. 1997

View full text Add to dashboard Cite

Subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in schizophrenia and dissociative states, including impaired performance of frontal lobe-sensitive tests. Several lines of evidence suggest that ketamine may impair PFC function in part by interacting with dopamine neurotransmission in this region. This study sought to determine the mechanism by which ketamine may disrupt dopaminergic neurotransmission in, and cognitive functions associated with, the PFC. A thorough dose-response study using microdialysis in conscious rats indicated that low doses of ketamine (10, 20, and 30 mg/kg) increase glutamate outflow in the PFC, suggesting that at these doses ketamine may increase glutamatergic neurotransmission in the PFC at non-NMDA glutamate receptors. An anesthetic dose of ketamine (200 mg/kg) decreased, and an intermediate dose of 50 mg/kg did not affect, glutamate levels. Ketamine, at 30 mg/kg, also increased the release of dopamine in the PFC. This increase was blocked by intra-PFC application of the AMPA/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione CNQX. Furthermore, ketamine-induced activation of dopamine release and impairment of spatial delayed alternation in the rodent, a PFC-sensitive cognitive task, was ameliorated by systemic pretreatment with AMPA/kainate receptor antagonist LY293558. These findings suggest that ketamine may disrupt dopaminergic neurotransmission in the PFC as well as cognitive functions associated with this region, in part, by increasing the release of glutamate, thereby stimulating postsynaptic non-NMDA glutamate receptors.Key words: microdialysis; phencyclidine; schizophrenia; working memory; antipsychotic drugs; AMPA receptors Recent clinical trials with ketamine, a noncompetitive antagonist of the NMDA receptor (Thomson et al., 1985), have demonstrated that subanesthetic doses of this drug exacerbate preexisting symptoms of schizophrenia (Lahti et al., 1995a,b) and produce behaviors in healthy individuals that bear a resemblance to a broad range of symptoms associated with schizophrenia, including impaired performance in psychological tests sensitive to prefrontal cortex (PFC) function (Ghoneim et al., 1985;Oye et al., 1992;Krystal et al., 1994; Malhorta et al., 1996). In agreement with clinical studies, basic findings indicate that subanesthetic doses of ketamine and other noncompetitive NMDA receptor antagonists produce deficits in acquisition and performance of cognitive tasks, including those that are sensitive to the functional integrity of the PFC (Danysz et al

show abstract

“…For example, intracortical infusions of cholinergic antagonists or dopaminergic agonists impaired the performance of a delayed matching to position (Broersen et al 1994;Herremans et al 1996;Zahrt et al 1997). Microinjections of D 1 antagonist SCH-23390 into the prelimbic region of the PFC disrupted performance of a delayed task but not a non-delayed task in a radial arm maze, suggesting that D 1 receptors in the PFC are involved in working memory processes (Seamans et al 1998).…”

Section: Introductionmentioning

confidence: 98%