Quetiapine and Buspirone Both Elevate Cortical Levels of Noradrenaline and Dopamine In vivo, but Do Not have Synergistic Effects

Abstract

Decreased cognitive ability is a significant problem in schizophrenia, and it has been proposed that augmentation of antipsychotics with 5HT1A receptor agonists may improve cognitive performance. Clinical studies have been mixed but there have been no studies specifically examining the effects of combining the atypical antipsychotic quetiapine with the 5HT1A receptor partial agonist, buspirone on monoamine release. This is of interest given previous evidence that monoamine release can alter cognition in schizophrenia. In the present study we measured in vivo levels of monoamines in the frontal cortex of Sprague Dawley rats and examined if buspirone (2.5 mg/kg i.p.), altered monoamine release both when given alone and when combined with quetiapine (10 mg/kg i.p.). We found that serotonin levels were not altered by either drug, either alone or in combination. In contrast, both buspirone and quetiapine monotherapy significantly increased release of noradrenaline (112 and 160% respectively) and dopamine (169 and 191% respectively) compared to controls. However, there were no additional increases in in vivo monoamine release when the combination of these drugs were given. One possible explanation for these negative findings could be that the intrinsic 5HT1A agonist activity of quetiapine on its own is of such significance that it is not further enhanced by buspirone. These findings do not support clinical studies combining buspirone and quetiapine, if these were to be used on the basis of enhanced monoamine neurotransmission. These findings may also have implications for the atypical antipsychotic drugs in development which combine dopamine D2 antagonism with 5HT1A partial agonism.

Human motoneurone excitability is depressed by activation of serotonin 1A receptors with buspirone

“…; Silverstone et al . ). However, because buspirone and its metabolite have opposing effects on the serotonergic and noradrenergic systems, indirect effects are difficult to predict.…”

Quetiapine attenuates cognitive impairment and decreases seizure susceptibility possibly through promoting myelin development in a rat model of malformations of cortical development

“…The present study demonstrates that postnatal administration of quetiapine prevents cognitive impairment in a rodent model of MCD, suggesting quetiapine may serve as a potential therapy for co-morbid behavioral disorders found in patients diagnosed with MCD. It has been proposed that increasing the release of both noradrenaline and dopamine (Silverstone et al, 2012), which affect hypothalamicpituitary-adrenal (HPA) axis activity, would reverse the BRES : 44350 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 62...…”

“…Procedures for drug administration, dose selection, and dosing interval were all based on previous studies (Silverstone et al, 2012). Animals were randomly assigned to one of three groups: (1) control group (n¼12), subjects derived from dams that had been placed into the chamber without X-ray irradiation on E17, and received saline i.p.…”

Efficacy of Low Adjunctive Quetiapine Administration in Control of Hypomanic State in Bipolar Affective Disorder Captured by EEG

“…In fact, quetiapine acts by blocking D1 and D2 receptors as reasonable for modifying psychotic states, whereby the metabolic norquetiapine with its antagonising actions of the 5HT2A and 5HT2C receptor seems to be predominately responsible for mood regulation by facilitating dopamine release at prefrontal cortex sites [1]. Moreover, quetiapine and norquetiapine show a high affinity also to 5HT1A with its property of increasing, among others, the serotonine neurotransmission of the raphe neurons as known as a crucial area of vigilance regulation [20]. Interestingly, quetiapine but to a greater degree the still neuroactive metabolic norquetiapine, show a high affinity for 5HT7 receptor, which is involved in depression and sleeprelated circadian rhythm disorders [21].…”