AMPA Receptor Stimulation within the Central Nucleus of the Amygdala Elicits a Differential Activation of Central Dopaminergic Systems

Abstract

Appetitive and aversive arousing stimuli increase rates of dopamine (DA) release, particularly within the prefrontal cortex (PFC). Evidence suggests an activating influence of both the central (CeA) and basolateral (BlA) nuclei of the amygdala on DA neurotransmission. For example, lesions of CeA block stressor-induced increases in DA release. Additionally, electrical stimulation of BlA increases DA release in select terminal fields. Previous studies indicate that glutamatergic AMPA receptors modulate CeA and BlA output. However, the extent to which AMPA receptors participate in amygdala-dependent activation of DA neurotransmission is unknown. The current studies examined the effects of bilateral AMPA infusions within CeA or BlA on post-mortem and in vivo microdialysis indices of DA release. Additionally, stress is associated with moderate increases in serotonin (5-HT) neurotransmission that are also blocked by CeA lesions. Thus, the current studies also examined the impact of AMPA infusions on post-mortem indices of 5-HT utilization. AMPA infusion into CeA, but not BlA, increased post-mortem indices of DA and 5-HT release in a pattern comparable to that observed under appetitive/aversive conditions. In vivo microdialysis studies confirmed that AMPA infusions into CeA, but not BlA, increase extracellular PFC DA levels. When infused into sleeping animals, CeA-AMPA infusion also elicited a rapid-onset transition into waking. Thus, CeA-AMPA receptors exert an excitatory influence on DA and 5-HT neurotransmission and on behavioral state. Combined, these results suggest that CeA-AMPA receptors may participate in the coordination of neural systems involved in the regulation of behavioral state under high-arousal conditions.

Mesocorticolimbic dopamine functioning in primary psychopathy: A source of within-group heterogeneity

“…In addition, PFC glutamatergic projections also heavily innervate the basolateral amygdala directly (nr. 13) (Cassell and Wright, 1986;Leichnetz et al, 1976), where, comparable to findings in the striatum (Grace, 1991), they might modulate tonic DA release rates through volume-transmission activation of glutamatergic receptors on presynaptic DA terminals (Ohmori et al, 1992;Walker and Davis, 2002;Sesack et al, 2003;Stalnaker and Berridge, 2003;Likhtik et al, 2005).…”

A comparison of neural responses to appetitive and aversive stimuli in humans and other mammals

“…Current data suggest that intra-central, but not basolateral, amygdala AMPA receptor stimulation may be involved in arousal and affective cue learning. Haney et al (2010) and Stalnaker and Berridge (2003) Some studies have found regionally-selective activations within the amygdala. For instance, c-Fos labelling suggested that medial CeA may be more involved in appetitive processing (for food-deprived rats in response to a cue signalling food, or water-deprived mice in a place preference task) while the BLA and lateral CeA may reflect salience processing.…”

AMPA Receptor Potentiators as Novel Antidepressants

“…Stalnaker and Berridge [139] presented evidence that AMPA receptors may play a facilitory role in coordinating responses to stressful or high arousal situations. Local infusions of AMPA into the central but not the basolateral amygdala increased dopamine in microdialysis perfusates, an effect that can be generated by applied external stressors.…”