Dopamine D2 receptors in the expression and extinction of contextual and cued conditioned fear in rats

Vita, Vivian M. de; Zapparoli, Heloisa R.; Reimer, Adriano E.; Brandão, Marcus Lira; Oliveira, Amanda Ribeiro de

doi:10.1007/s00221-021-06116-6

Cited by 13 publications

(28 citation statements)

References 83 publications

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“…The protocol used for acquisition, expression, and extinction of contextual conditioned fear was effective for both males and females. This result is in line with other studies from our group obtained using a similar protocol in male rats only (De Souza Caetano et al, 2013;De Vita et al, 2021) and extends the validity of our protocol to female rats. We did not verify differences between the sexes or estrous cycle phases for the expression and extinction of conditioned freezing, although same-context females continue to freeze more in the retest than different-context females.…”

Section: Discussionsupporting

confidence: 93%

“…In male rats, besides recently confirming the involvement of D2-like receptor-mediated mechanisms in the expression of conditioned fear, our previous results have suggested that D2-like receptors are not involved in conditioned freezing extinction (De Vita et al, 2021). In the present study, sulpiride administered to females in proestrus/estrus during the test session did not affect the freezing behavior exhibited 24 h later, during the retest session.…”

Section: Discussionsupporting

confidence: 84%

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Involvement of D2-like dopaminergic receptors in contextual fear conditioning in female rats: influence of estrous cycle

Alves

Reimer

Oliveira

2022

Front. Behav. Neurosci.

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Introduction: Dopamine has been increasingly recognized as a key neurotransmitter regulating fear/anxiety states. Nevertheless, the influence of sex and estrous cycle differences on the role of dopamine in fear responses needs further investigation. We aimed to evaluate the effects of sulpiride (a dopaminergic D2-like receptor antagonist) on contextual fear conditioning in females while exploring the influence of the estrous cycle.Methods: First, using a contextual fear conditioning paradigm, we assessed potential differences in acquisition, expression, and extinction of the conditioned freezing response in male and female (split in proestrus/estrus and metestrus/diestrus) Wistar rats. In a second cohort, we evaluated the effects of sulpiride (20 and 40 mg/kg) on contextual conditioned fear in females during proestrus/estrus and metestrus/diestrus. Potential nonspecific effects were assessed in motor activity assays (catalepsy and open-field tests).Results: No sex differences nor estrous cycle effects on freezing behavior were observed during the fear conditioning phases. Sulpiride reduced freezing expression in female rats. Moreover, females during the proestrus/estrus phases of the estrous cycle were more sensitive to the effects of sulpiride than females in metestrus/diestrus. Sulpiride did not cause motor impairments.Discussion: Although no sex or estrous cycle differences were observed in basal conditioned fear expression and extinction, the estrous cycle seems to influence the effects of D2-like antagonists on contextual fear conditioning.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 84%

Involvement of D2-like dopaminergic receptors in contextual fear conditioning in female rats: influence of estrous cycle

Alves

Reimer

Oliveira

2022

Front. Behav. Neurosci.

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“…Sulpiride has been reported to facilitate extinction learning in mice ( Ponnusamy et al, 2005 ), but another study has found attenuated fear extinction after sulpiride injection into the rat amygdala ( Shi et al, 2017 ). These divergent findings ( Ponnusamy et al, 2005 ; Yim et al, 2009 ; Dubrovina and Zinov’eva, 2010 ; Mueller et al, 2010 ; Stockhorst and Antov, 2015 ; Shi et al, 2017 ) may be explained by a recent study in rats suggesting that sulpiride can reduce fear expression but has no effect on acquisition/extinction learning ( de Vita et al, 2021 ). Furthermore, depending on the chosen dose, sulpiride can lead to opposing effects due to pre- vs postsynaptic actions ( Holmes and Quirk, 2010 ; Crockett and Fehr, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Alpha-2 Adrenoreceptor Antagonist Yohimbine Potentiates Consolidation of Conditioned Fear

Sperl

Panitz

Skoluda

et al. 2022

International Journal of Neuropsychopharmacology

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Background Hyperconsolidation of aversive associations and poor extinction learning have been hypothesized to be crucial in the acquisition of pathological fear. Previous animal and human research points to the potential role of the catecholaminergic system, particularly noradrenaline and dopamine, in acquiring emotional memories. Here, we investigated in a between-subjects design with three groups whether the noradrenergic alpha-2 adrenoreceptor antagonist yohimbine and the dopaminergic D2-receptor antagonist sulpiride modulate long-term fear conditioning and extinction in humans. Methods Fifty-five healthy male students were recruited. The final sample consisted of N=51 participants who were explicitly aware about the CS–US contingencies after fear acquisition. The participants were then randomly assigned to one of the three groups and received either yohimbine (10mg, n=17), sulpiride (200mg, n=16), or placebo (n=18) between fear acquisition and extinction. Recall of conditioned (non-extinguished CS+ versus CS-) and extinguished fear (extinguished CS+ versus CS-) was assessed one day later, while a 64-channel electroencephalogram (EEG) was recorded. Results The yohimbine group showed increased salivary alpha-amylase activity, confirming a successful manipulation of central noradrenergic release. Elevated fear-conditioned bradycardia and larger differential amplitudes of the N170 and LPP components in the event-related brain potential indicated that yohimbine treatment (compared with a placebo and sulpiride) enhanced fear recall during day 2. Conclusions These results suggest that yohimbine potentiates cardiac and central electrophysiological signatures of fear memory consolidation. They thereby elucidate the key role of noradrenaline in strengthening the consolidation of conditioned fear associations, which may be a key mechanism in the etiology of fear-related disorders.

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“…These findings suggest that emotional behavior may be regulated by the interaction between PSA-NCAM and TRPC1, −4, and −5 and by the PSA- and NCAM-dependent Ca 2+ entry via TRPC1, -4, and -5. Moreover, these interactions and the Ca 2+ influx may influence the interaction of the dopamine D2 receptor with NCAM180 and TRPC1, −4, or −5 [ 50 , 51 ] and thus could influence dopamine D2 receptor activity and dopamine-regulated emotional behavior including fear conditioning [ 81 , 82 , 83 ]. Impairments in the interplay among PSA-NCAM, dopamine D2 receptor, and TRPC1, −4, and −5 may lead to NCAM-and dopamine D2 receptor-associated psychiatric disorders, such as schizophrenia, bipolar disorder, depression, and anxiety disorder [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Interactions between the Polysialylated Neural Cell Adhesion Molecule and the Transient Receptor Potential Canonical Channels 1, 4, and 5 Induce Entry of Ca2+ into Neurons

Amores-Bonet

Kleene

Theis

et al. 2022

IJMS

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The neural cell adhesion molecule (NCAM) plays important functional roles in the developing and mature nervous systems. Here, we show that the transient receptor potential canonical (TRPC) ion channels TRPC1, −4, and −5 not only interact with the intracellular domains of the transmembrane isoforms NCAM140 and NCAM180, but also with the glycan polysialic acid (PSA) covalently attached to the NCAM protein backbone. NCAM antibody treatment leads to the opening of TRPC1, −4, and −5 hetero- or homomers at the plasma membrane and to the influx of Ca2+ into cultured cortical neurons and CHO cells expressing NCAM, PSA, and TRPC1 and −4 or TRPC1 and −5. NCAM-stimulated Ca2+ entry was blocked by the TRPC inhibitor Pico145 or the bacterial PSA homolog colominic acid. NCAM-stimulated Ca2+ influx was detectable neither in NCAM-deficient cortical neurons nor in TRPC1/4- or TRPC1/5-expressing CHO cells that express NCAM, but not PSA. NCAM-induced neurite outgrowth was reduced by TRPC inhibitors and a function-blocking TRPC1 antibody. A characteristic signaling feature was that extracellular signal-regulated kinase 1/2 phosphorylation was also reduced by TRPC inhibitors. Our findings indicate that the interaction of NCAM with TRPC1, −4, and −5 contributes to the NCAM-stimulated and PSA-dependent Ca2+ entry into neurons thereby influencing essential neural functions.

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Dopamine D2 receptors in the expression and extinction of contextual and cued conditioned fear in rats

Cited by 13 publications

References 83 publications

Involvement of D2-like dopaminergic receptors in contextual fear conditioning in female rats: influence of estrous cycle

Involvement of D2-like dopaminergic receptors in contextual fear conditioning in female rats: influence of estrous cycle

Alpha-2 Adrenoreceptor Antagonist Yohimbine Potentiates Consolidation of Conditioned Fear

Interactions between the Polysialylated Neural Cell Adhesion Molecule and the Transient Receptor Potential Canonical Channels 1, 4, and 5 Induce Entry of Ca2+ into Neurons

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