Blocking Opioid Receptors in a Songbird Cortical Region Modulates the Acoustic Features and Levels of Female-Directed Singing

Abstract

The organization of the anterior forebrain pathway (AFP) of songbirds important for context-dependent singing is similar to that of cortical basal ganglia loops (CBG) in mammals, which underlie motor behaviors including vocalization. Since different components of the AFP express high levels of µ-opioid receptors (µ-ORs) as do CBG loops, songbirds act as model systems to study the role of opioid modulation on vocalization and the motivation to sing. The AFP in songbirds includes the cortical/pallial region LMAN (lateral magnocellular nucleus of the anterior nidopallium) which projects to Area X, a nucleus of the avian basal ganglia. In the present study, microdialysis was used to infuse different doses of the opioid antagonist naloxone in LMAN of adult male zebra finches. Whereas all doses of naloxone led to significant decreases in the number of FD (female-directed) songs, only 100 and 200 ng/ml of naloxone affected their acoustic properties. The decrease in FD song was not accompanied by changes in levels of attention toward females or those of neurotransmitters (dopamine, glutamate, and GABA) in LMAN. An earlier study had shown that similar manipulations in Area X did not lead to alterations in the number of FD songs but had significantly greater effects on their acoustic properties. Taken together, our results suggest that there are reciprocal effects of OR modulation on cortical and basal ganglia components of the AFP in songbirds.

The Role of the Endogenous Opioid System in the Vocal Behavior of Songbirds and Its Possible Role in Vocal Learning

“…Earlier studies (Khurshid et al, 2010;Kumar et al, 2019Kumar et al, , 2020) have demonstrated that the opioid system can modulate different aspects of singing. Based on the neuroanatomical localization of ORs in the song control areas of oscines, it is possible that these receptors may be involved in vocal learning (Gulledge and Deviche, 1999).…”

“…Recent studies have shown that blocking ORs with naloxone specifically in components of the AFP, as opposed to systemic injections, led to changes in the motivation to sing as well as those in the acoustic features of FD songs in adult male zebra finches ( Kumar et al, 2019 , 2020 ). Infusions of naloxone into LMAN ( Kumar et al, 2019 ) resulted in a significant decrease in the number of FD songs ( Kumar et al, 2020 ). Blocking ORs in both LMAN and Area X led to significant decreases in the length of motifs produced during FD song.…”

“…Blocking ORs in both LMAN and Area X led to significant decreases in the length of motifs produced during FD song. Whereas blocking ORs in LMAN led to significant decreases in the amplitude modulation of motifs at a specific dose (100 ng/ml) of naloxone ( Kumar et al, 2019 ), the same manipulation in Area X led to significant decreases in frequency and amplitude modulation and pitch goodness as well as a significant increase in pitch ( Kumar et al, 2020 ). Additionally, blocking ORs in LMAN and Area X led to changes in the spectral quality of individual syllables in directed songs.…”

The expression of delta opioid receptor mRNA in adult male zebra finches (Taenopygia guttata)

“…We were interested in studying the expression of δ-ORs in zebra finches ( Taenopygia guttata ), a species of songbirds widely used as a model system to study the interactions between neural circuits and behavior [ 26 , 27 ]. As seen in humans, songbirds learn their vocalizations during a sensitive period from a song model (generally, their fathers) and their songs are used as a mode for communication, courtship behavior, individual recognition and aggression [ 28 – 30 ].…”

“…An earlier study demonstrated that blocking ORs using the general opioid antagonist naloxone systemically leads to a decrease in directed and undirected songs and their spectro-temporal properties in adult male zebra finches [ 40 ]. Additionally, site-specific injections of naloxone in the anterior forebrain pathway of the song control system leads to changes in the number and acoustic features of female-directed song [ 10 , 27 ]. Preliminary data from our lab has additionally demonstrated that blocking δ-ORs in adult birds leads to a decrease in female-directed singing and a slight decrease in song length but no major changes in the spectro-temporal properties of song [ 41 ].…”