Infusion of the dopamine D1 receptor antagonist SCH 23390 into the amygdala blocks fear expression in a potentiated startle paradigm

Lamont, Elaine Waddington; Kokkinidis, Larry

doi:10.1016/s0006-8993(98)00281-9

Cited by 117 publications

(84 citation statements)

References 61 publications

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“…Secondly, immunohistochemical data corroborate the finding that DA activity is elevated in the amygdala during Pavlovian conditioning and during instrumental conditioning (Phillips et al, 2003). Thirdly, in fear-related paradigms, SCH-23390 infusions into the CeA or BLA block acquisition and performance of fear-potentiated startle (Greba and Kokkinidis, 2000;Lamont and Kokkinidis, 1998), impair second-order fear conditioning (Nader and LeDoux, 1999), and modulate responses to stress (Stevenson and Gratton, 2004). Lastly, addiction-related studies show that amygdalar D1 activation is involved in drug conditioning and self-administration (Caine et al, 1995;Di Ciano and Everitt, 2004;Zarrindast et al, 2003).…”

Section: Da In the Amygdala Mediates The Acquisition Of Significance supporting

confidence: 66%

Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala

2005

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Substantial experimental evidence exists suggesting a critical role for dopamine in reinforcer-related processes, such as learning and drug addiction. Dopamine receptors, and in particular D1 receptors, are widely considered as modulators of synaptic plasticity. The amygdala contains both dopamine terminals and dopamine D1 receptors and is intimately involved in motivation and learning. However, little is known about the involvement of D1 receptor activation in two subnuclei of the mammalian amygdala, the central nucleus and basolateral complex in instrumental learning. Following recovery from surgery and preliminary training, rats with bilateral indwelling cannulae aimed at the central nucleus or basolateral complex were trained to lever-press for sucrose pellets over 12 sessions. Infusion of the selective D1 antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (0.3 nmol and 3.0 nmol) prior to the first five training sessions dose-dependently impaired instrumental learning when compared with vehicleinfused controls. All rats were then exposed to five sessions drug-free; lever-pressing quickly reached equal levels across groups. A drug infusion prior to an 11th session revealed no effect on performance. Control experiments indicated that basic motivational processes and general motor responses were intact, such as spontaneous feeding and locomotor activity. These results show an essential role for D1-receptor activation in both the central nucleus and basolateral complex on the acquisition of lever pressing for sucrose pellets in rats, but not the performance of the behavior once conditioned. We propose that instrumental learning is dependent on plasticity in the central nucleus and basolateral complex amygdala, and that D1 receptor activation participates in transcriptional processes that underlie this plasticity.Keywords instrumental learning; amygdala; dopamine; D1; plasticity; rats Biologically important events, such as procurement of food, escape from predation, and access to sexual partners, often require flexible patterns of behavior in order to produce themforaging, vigilance, and defense, for example. Important biological reinforcers (Reinf), in turn, change the behavior that produced them, illustrating a form of adaptability termed "instrumental learning." Many Reinf-related processes are mediated by the mesocorticolimbic dopamine (DA) system, consisting of DA neurons in the ventral tegmental area and their projections to the nucleus accumbens, medial prefrontal cortex, striatum, amygdala and other *Corresponding author. Tel: +1-608-262-9332. E-mail address: mandrzejewsk@wisc.edu (M. E. Andrzejewski). (Beninger and Miller, 1998;Cardinal et al., 2002;Kelley and Berridge, 2002). Specifically, studies have shown that D1 receptor activation throughout this corticolimbicstriatal network plays a critical role in learning (Beninger and Gerdjikov, 2004). Indeed, D1 receptor activation is thought to serve a crucial modulatory function in the induction o...

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Section: Da In the Amygdala Mediates The Acquisition Of Significance supporting

confidence: 66%

Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala

2005

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“…Along these lines, several reports have shown that the BST and, more generally, the extended amygdala, is involved in a number of stress-and anxiety-like behaviors (Walker et al, 2003), including those directly mediated by CRF (Erb and Stewart, 1999;Jasnow et al, 2004) and DA (Lamont and Kokkinidis, 1998;de la Mora et al, 2005). Together, these data suggest that DA-CRF interactions in the extended amygdala could be an important mechanism in the control of mood states.…”

Section: Discussionmentioning

confidence: 82%

Behavioral and Anatomical Interactions between Dopamine and Corticotropin-Releasing Factor in the Rat

Meloni¹,

Gerety²,

Knoll³

et al. 2006

J. Neurosci.

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“…Our finding, that 2WAA is absent in vrDD mice when DA signaling is restored to the striatum alone, but intact when restored to both amygdala and striatum, is strong evidence for an interaction of DA signaling in these two brain regions. Pavlovian conditioning experiments have demonstrated that DA signaling in the amygdala is crucial for the establishment of associations between the conditioned stimulus and an aversive unconditioned event (Lamont and Kokkinidis 1998;Greba et al 2001;Pezze and Feldon 2004;de Oliveira et al 2009;Fadok et al 2009). DD mice are unable to learn a fear-potentiated startle response, but it can be restored with either L-Dopa or viral restoration of DA signaling in the VTA (Fadok et al 2009) or NAc and amygdala (Fadok et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Besides its involvement in drug-seeking, motor control, reward-learning, motivation, and attentional processes (Dayan and Balleine 2002;Schultz 2002;Dalley et al 2004;Wise 2004), the dopamine (DA) system has also been associated with fearrelated learning (Lamont and Kokkinidis 1998;Greba et al 2001;Pezze and Feldon 2004;de Oliveira et al 2009;Fadok et al 2009). DA neurons that are important for these behaviors reside predominantly in the substantia nigra pars compacta (SNc), which projects mainly to the dorsal striatum (caudate putamen, CPu), and the ventral tegmental area (VTA), which projects to the ventral striatum (nucleus accumbens, NAc), medial part of the CPu, and to cortical and limbic areas (Bjorklund and Dunnett 2007).…”

Section: Introductionmentioning

confidence: 99%

Requirement of dopamine signaling in the amygdala and striatum for learning and maintenance of a conditioned avoidance response

Darvas¹,

Fadok²,

Palmiter³

2011

Learn. Mem.

117

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Two-way active avoidance (2WAA) involves learning Pavlovian (association of a sound cue with a foot shock) and instrumental (shock avoidance) contingencies. To identify regions where dopamine (DA) is involved in mediating 2WAA, we restored DA signaling in specific brain areas of dopamine-deficient (DD) mice by local reactivation of conditionally inactivated Th genes using viral gene therapy. Among all targeted areas-prefrontal cortex (PFC), amygdala, ventral striatum, dorsal striatum, and whole striatum-only restoration of DA signaling to both the whole striatum together with the amygdala enabled DD mice to acquire 2WAA. However, after prolonged overtraining during which DD mice had DA synthesis systemically reconstituted pharmacologically with L-3,4-dihydroxyphenylalanine (L-Dopa), DA signaling in the striatum alone was sufficient to maintain 2WAA, whereas DA signaling in the PFC together with the amygdala was insufficient to maintain 2WAA. Our results indicate that learning 2WAA requires DA signaling in both the amygdala and the entire striatum; however, after sufficient training, DA signaling in the striatum alone can maintain the learned avoidance behavior.

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Infusion of the dopamine D1 receptor antagonist SCH 23390 into the amygdala blocks fear expression in a potentiated startle paradigm

Cited by 117 publications

References 61 publications

Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala

Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala

Behavioral and Anatomical Interactions between Dopamine and Corticotropin-Releasing Factor in the Rat

Requirement of dopamine signaling in the amygdala and striatum for learning and maintenance of a conditioned avoidance response

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