Nitric oxide modulates dopaminergic regulation of prepulse inhibition in the basolateral amygdala

Abstract

Systemic injection of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (LNO) prevents the disruptive effect of amphetamine (Amph) on prepulse inhibition (PPI), a sensorimotor gating model in which the amplitude of the acoustic startle response (ASR) to a startling sound (pulse) is reduced when preceded immediately by a weaker stimulus (prepulse). Given that dopamine (DA) projections to the basolateral amygdala (BLA) are involved in the control of information processing, our aim was to investigate if intra-BLA administration of LNO would modify the disruption caused by the DA agonists, Amph, apomorphine (Apo) and quinpirole (QNP), on PPI. Male Wistar rats received bilateral intra-BLA microinjections (0.2 µL/min/side) of combined treatments (saline or LNO 11 µg followed by saline, QNP 3 µg, Apo 10 µg or Amph 30 µg). PPI was disrupted by intra-BLA Apo, QNP or Amph but not by LNO. Prior bilateral intra-BLA injection of LNO prevented the Apo- and QNP-induced disruption of PPI but did not affect that caused by Amph. APO- or QNP-induced increases in ASR to prepulse + pulse were also restored by LNO. Since local inhibition of NO formation affected the effects of direct, but not indirect, DA agonists, the results suggest that this modulation is not occurring at the level of DA release but may involve complex interactions with other neurotransmitter systems.

A Computational Model for the Simulation of Prepulse Inhibition and Its Modulation by Cortical and Subcortical Units

“…The simulation of dopaminergic agonists in the systemic test, in amygdala, or in NAc caused a decrease in the %PPI. Similar results are shown in studies with the administration of dopaminergic drugs in rats by systemic injection [22,23,62], intra-amygdala [18], or intra-NAc [20,26,27]. In contrast, the simulation of the dopaminergic antagonists produced a slight increase in the %PPI.…”

“…A study conducted by Stevenson and Gratton [19] detected a reduction in the %PPI by injecting raclopride (a D 2 antagonist) in a rat's amygdala. As detailed above, the amygdala model implemented in the present work was based on rat studies [14] with different strains (Wistar and Sprague-Dawley) [18,22], while the the study of Stevenson and Gratton [19] used the Long-Evans strain. Since there are differences in the effect of amphetamine between Sprague-Dawley and Long-Evans [26], the difference detected in the simulation of D 2 antagonist with the study of Stevenson and Gratton could be attributed to the distinct strains used to implement the present model.…”

“…Dopaminergic receptors are expressed in the amygdala, prefrontal cortex, and striatum [12][13][14][15][16][17]. Administration of dopaminergic agonists into the rat amygdala [18,19], nucleus accumbens [20], or via systemic injection [18,[21][22][23] affects PPI. Because dopamine signals stimulus salience to the nucleus accumbens [24], it may be linked to regulating the flow of information to other brain regions by controlling sensorimotor gating [22,25].…”

Hippocampal ether-à-go-go1 potassium channels blockade: Effects in the startle reflex and prepulse inhibition

“…PPI refers to the reduction in the startle magnitude to a startling acoustic stimulus 'pulse' when it is shortly preceded by a weaker 'prepulse' stimulus [35]. Startle response and PPI were conducted simultaneously in two identical startle systems (Med Associates, Inc., USA) as described before [30].…”

Avaliação da associação de canabidiol e nitroprussiato de sódio no prejuízo sensório-motor induzido pelo tratamento agudo com MK-801

“…Sobretudo, é importante ressaltar que todas as teorias propostas envolvem vias interconectadas, e é provável que em muitas diferentes formas de psicose, mais de uma dessas vias está envolvida (DEAN, 2017). PENGLEE et al, 2021;SALUM et al, 2011).…”