Cognitive effects of dopaminergic and glutamatergic blockade in nucleus accumbens in pigeons

Abstract

In earlier studies it was found that glutamatergic transmission within the nucleus accumbens septi is involved in the performance of a learned visual shape discrimination in pigeons. This study examines what effects several kinds of glutamate and dopamine antagonists have on the same task. Pigeons were trained with the relevant discrimination, bilaterally implanted with cannulas into the nucleus accumbens and tested after various transmission blockers had been administered intracerebrally. SCH-23390, a D1 dopamine antagonist, at the dose used, had no effect, and Spiperone, a D2-dopamine and 5HT2a-serotonine antagonist, significantly decreased the error repeat trials. CNQX, a non-NMDA glutamate receptor antagonist, and Cycloleucine, an antagonist of the glycine allosteric site of NMDA receptors, had no effect. CGS-19755, a selective competitive NMDA antagonist, significantly impaired performance by significantly decreasing the percent correct trials and increasing the error repeat trials. CPPG, a II/III metabotropic glutamate antagonist, remarkably improved performance. MMPG, a III/II metabotropic glutamate antagonist, at the dose used, did not have any significant effect. The preparation employed may be a useful animal model of perceptual disturbances in schizophrenia.

Differential behavioral profile induced by the injection of dipotassium chlorazepate within brain areas that project to the nucleus accumbens septi

“…in animals, suggesting that a glutamatergic dysfunction within NAS is related to positive [2,21,[23][24][25]45] and negative [23,24,44] symptoms, and also, to working memory schizophrenic dysfunction [4]. These later findings are in accordance with the fact that NAS is considered today a switchboard for goaldirected behaviors [32].…”

Effects of metabotropic glutamate receptor 2/3 agonism and antagonism on schizophrenia-like cognitive deficits induced by phencyclidine in rats

“…This approach was further supported by reports of pro-cognitive effects of metabotropic glutamate receptor 2/3 antagonists in some studies (Gargiulo et al, 2005; Higgins et al, 2004). Repeated phencyclidine administration significantly decreased accuracy ( F (1,18) = 18.64, P < 0.001; Fig.…”

“…However, other studies reported that metabotropic glutamate receptor 2/3 antagonists improved acquisition of a spatial memory task and visual discrimination (Gargiulo et al, 2005; Higgins et al, 2004), again showing that different cognitive modalities are differentially affected by a given compound. Previous studies have reported exacerbation of phencyclidine-induced hyperlocomotion by LY341495 (Rorick-Kehn et al, 2007), but few studies have examined the effects of LY341495 or other metabotropic glutamate receptor 2/3 antagonists on cognitive disruptions induced by phencyclidine or other NMDA receptor antagonists.…”

“…However, findings have been inconsistent, with other studies finding no improvement of NMDA receptor antagonist-induced cognitive deficits after metabotropic glutamate receptor 2/3 agonist treatment (Ossowska et al, 2000; Schlumberger et al, 2009) or even impairment of baseline cognitive performance by metabotropic glutamate receptor 2/3 agonists (Higgins et al, 2004). Moreover, cognitive enhancement has been observed after treatment with metabotropic glutamate receptor 2/3 antagonists in some studies (Gargiulo et al, 2005; Higgins et al, 2004). The present study therefore further explored the effects of metabotropic glutamate receptor 2/3 manipulation on cognitive performance.…”

Effects of post-training administration of LY341495, as a mGluR2/3 antagonist on spatial memory deficit in rats fed with high-fat diet

“…Group II receptors are located mainly in presynaptic terminals (10) and are highly expressed in CNS areas related to learning and memory, such as the hippocampus, amygdala, and prefrontal cortex (PFC) (11,12). Moreover, cognitive enhancement has been observed after treatment with metabotropic glutamate receptor 2/3 antagonists and glutamatergic blockade in some studies (13,14). The present study therefore further 4 explored the effects of metabotropic glutamate receptor 2/3 manipulation on cognitive performance.…”