Effect of antipsychotic drugs and selective dopaminergic antagonists on dopamine-induced facilitatory activity in prelimbic cortical pyramidal neurons. An in vitro study

Dopamine D1versus D4Receptors Differentially Modulate the Encoding of Salient versus Nonsalient Emotional Information in the Medial Prefrontal Cortex

“…However, bilateral intra-mPFC microinfusions of quinpirole at a higher (nonspecific) dose (1000 ng/0.5 l) resulted in a potentiation of subthreshold fear stimuli as demonstrated by a significant increase in the time spent freezing to the CSϩ relative to the CSϪ. tent with anatomical and electrophysiological evidence showing higher relative concentrations of the D 4 subtype and greater neuronal sensitivity within the mPFC to DA D 4 receptor activation, relative to other DA receptor subtypes (Mrzljak et al, 1996;Ceci et al, 1999;Wedzony et al, 2000;Onn et al, 2005).…”

“…Given the ability of D 4 receptor activation to amplify DAmediated neuronal activity within the mPFC (Ceci et al, 1999), we hypothesized that activation of mPFC D 4 receptors may potentiate the emotional salience of normally subthreshold sensory stimuli, leading to heightened emotional memory encoding. Our results demonstrate that activation of mPFC D 4 receptors potentiates the emotional salience of subthreshold fear-conditioning stimuli during acquisition but not expression (recall) phases of associative learning.…”

“…Functionally, DA transmission within the mPFC influences neuronal network activity in a biphasic manner, with D 1 receptor activation increasing the intrinsic excitability of inhibitory GABAergic interneurons and D 2 -like receptor activation decreasing the activity of these interneurons, presumably leading to decreased probability of tonic inhibitory GABA release within the mPFC (Seamans et al, 2001). The D 4 subtype is expressed highly in mPFC relative to other brain regions and plays a critical role in modulating neuronal activity in both prelimbic and infralimbic mPFC regions (Ceci et al, 1999;Onn et al, 2005). Additional support for a modulatory role of DA D 4 receptor transmission is suggested by findings that DA-mediated amplification of mPFC neuronal activity is preferentially mediated through dopaminergic actions on the D 4 receptor subtype (Ceci et al, 1999).…”

“…The D 4 subtype is expressed highly in mPFC relative to other brain regions and plays a critical role in modulating neuronal activity in both prelimbic and infralimbic mPFC regions (Ceci et al, 1999;Onn et al, 2005). Additional support for a modulatory role of DA D 4 receptor transmission is suggested by findings that DA-mediated amplification of mPFC neuronal activity is preferentially mediated through dopaminergic actions on the D 4 receptor subtype (Ceci et al, 1999). Given the critical role of the mPFC in the encoding and expression of emotionally salient information and its ability to amplify dopaminergic effects within mPFC neuronal networks, one possibility is that DA D 4 receptor activation within the mPFC may amplify the emotional salience of sensory information and the subsequent encoding of this associative information.…”

Dopamine D1 and D4 Receptor Subtypes Differentially Modulate Recurrent Excitatory Synapses in Prefrontal Cortical Pyramidal Neurons

“…Evidence for an inhibitory action of D2-D4 receptors in the frontal cortex is derived from studies in which D4-deficient mice exhibit spontaneous hyperexcitability in PFC pyramidal neurons (Rubinstein et al, 2001); however, this could be due to enhanced expression of NMDA and D1 receptors in D4 knockout mice (Gan et al, 2004). In contrast, a D2 subtype (D4)-mediated DA facilitatory action on membrane excitability in PFC pyramidal neurons was also reported (Ceci et al, 1999), and D4 receptor activation decreases GABA A receptor-mediated synaptic currents in dissociated prefrontal pyramidal neurons (Wang et al, 2002). Thus, there is no consensus as to which DA receptor subtype is involved in the inhibitory action of DA on PFC neuron excitability.…”