Dopamine-sensitive signaling mediators modulate psychostimulant-induced ultrasonic vocalization behavior in rats

Abstract

The mesolimbic dopamine system plays a major role in psychostimulant-induced ultrasonic vocalization (USV) behavior in rodents. Within this system, psychostimulants elevate synaptic concentrations of dopamine thereby leading to exaggerated activation of postsynaptic dopamine receptors within the D1-like and D2-like subfamilies. Dopamine receptor stimulation activate several transmembrane signaling systems and cognate intracellular mediators; downstream activation of transcription factors then conveys the information from receptor activation to appropriate modulation of cellular and physiologic functions. We previously showed that cocaine-induced USV behavior was associated with enhanced expression of the neurotrophin BDNF. Like cocaine, amphetamine also increases synaptic dopamine levels, albeit primarily through facilitating dopamine release. Therefore, in the present study we investigated whether amphetamine and cocaine similarly activate dopamine -linked signaling cascades to regulate intracellular mediators leading to induction of USV behavior. The results show that amphetamine increased the emission of 50 kHz USVs and this effect was blocked by SCH23390, a D1 receptor antagonist. Similar to cocaine, amphetamine increased BDNF protein expression in discrete brain regions, while pretreatment with K252a, a trkB neurotrophin receptor inhibitor, significantly reduced amphetamine-induced USV behavior. Inhibition of cyclic- AMP/PKA signaling with H89 or inhibition of PLC signaling with U73122 significantly blocked both the acute and subchronic amphetamine-induced USV behavior. In contrast, pharmacologic inhibition of either pathway enhanced cocaine-induced USV behavior. Although cocaine and amphetamine similarly modulate neurotrophin expression and USV, the molecular mechanisms by which these psychostimulants differentially activate dopamine receptor subtypes or other monoaminergic systems may be responsible for the distinct aspects of behavioral responses.

Poor sensitization of 50-kHz vocalization response to amphetamine predicts rat susceptibility to self-administration of the drug

“…In contrast to the earlier study, this failure cannot be attributed to the use of weak extinguishing methods or to comparisons of dissimilar, neurobiologically dissociable activities. Instead, the present data provide additional evidence that differences may be attributed to the differences between the mechanisms of action for AMPH and cocaine (Vanderschuren and Kalivas 2000 ; Williams and Undieh 2016 ), rendering NAC ineffective for AMPH abuse.…”

Developmental Vitamin D Deficiency Produces Behavioral Phenotypes of Relevance to Autism in an Animal Model

“…DA D 2 receptor knockout offspring exhibit reduced USVs in response to isolation from the dam [53]. Consistent with this elevating DA levels using amphetamine increased USVs in adult rats and this effect was blocked by halobenzazepine, a DA D1 receptor antagonist [54].…”

Measuring mania‐like elevated mood through amphetamine‐induced 50‐kHz ultrasonic vocalizations in rats

“…Corroborating evidence was obtained by Williams and Undieh (2016) who reported that systemic administration of the D1-receptor antagonist SCH-23390 prevented AMPH-induced 50-kHz USV. Moreover, de Oliveira Guaita et al ( 2018) replicated the inhibition of AMPH-induced 50-kHz USV by haloperidol but did not obtain evidence for prominent effects on the prevalence of 50-kHz USV subtypes.…”