Anticipatory 50kHz ultrasonic vocalizations are associated with escalated alcohol intake in dependent rats

Abstract

Rats emit 50 kHz ultrasonic vocalizations (USVs) in situations of increased motivation, such as during the anticipation of palatable food or drugs of abuse. Whether the same holds true for the anticipation of alcohol intake remains unknown. Alcohol drinking in a nondependent state is thought to be mediated by its rewarding effects (positive reinforcement), whereas drinking in the dependent state is motivated by alcohol’s stress-relieving effects (negative reinforcement). Here, we measured context-elicited 50 kHz USVs in alcohol-dependent (alcohol vapor-exposed) and nondependent rats immediately before operant alcohol self-administration sessions. Dependent rats showed escalated levels of alcohol intake compared with nondependent rats. Overall, dependent and nondependent rats showed similar levels of anticipatory 50 kHz USVs. However, the number of anticipatory USVs was positively correlated with alcohol intake in dependent rats but not nondependent rats. Additionally, dependent rats with higher alcohol intake displayed increased anticipatory 50 kHz USVs compared with rats that had lower alcohol intake, whereas no difference was observed between rats with high and low alcohol intake in the nondependent group. Increased 50 kHz USVs were specific for the anticipation of alcohol self-administration and did not generalize to a novel environment. These findings suggest that anticipatory 50 kHz USVs may be an indicator of context-elicited negative reinforcement learning.

Effects of ethanol exposure and withdrawal on dendritic morphology and spine density in the nucleus accumbens core and shell

“…We also note that behavioral outcomes were not assessed in the present study to avoid potentially complicating interpretation of the results, as behavioral testing/experience could influence dendritic morphology and spine density. Passive ethanol exposure via vapor chambers as performed here has repeatedly yielded behavioral signs of withdrawal and physical dependence (Lack et al, 2007; Macey et al, 1996; Roberts et al, 1996) as well as increased ethanol seeking/consumption (Buck et al, 2014; Roberts et al, 2000) and anxiety (Lack et al, 2007; Rassnick et al, 1993; Valdez et al, 2004). Whether these behavioral outcomes are related to the specific patterns of morphological alteration observed here represents an important topic for future research.…”

“…This exposure protocol yields blood ethanol concentrations in the 150–200mg/dL (0.15–0.20) range, produces robust physical dependence, and increases in anxiety-like behaviors (Lack, Diaz, Chappell, DuBois, & McCool, 2007) that are accompanied by significant alterations in glutamatergic and GABAergic neurotransmission in the amygdala (Christian, Alexander, Diaz, Robinson, & McCool, 2012; Diaz, Christian, Anderson, & McCool, 2011). Further, passive vaporized ethanol exposure protocols similar to that employed here induce conspicuous signs of withdrawal (e.g., tremor) upon removal of ethanol (Macey, Schulteis, Heinrichs, & Koob, 1996; Roberts, Cole, & Koob, 1996), anxiety (Rassnick, Heinrichs, Britton, & Koob, 1993; Valdez, Sabino, & Koob, 2004), increased tolerance for the hypothermic effects of ethanol (Ristuccia & Spear, 2005), reduced seizure thresholds (Ferko & Bobyock, 1977), and enhancements of subsequent ethanol seeking and operant self-administration (Buck, Malavar, George, Koob, & Vendruscolo, 2014; Roberts, Heyser, Cole, Griffin, & Koob, 2000). Following the withdrawal period (1 day or 7 days) or control exposure the brains were extracted for Golgi-Cox staining (Gibb & Kolb, 1998) and dendritic length, branching, overall spine density, and density of specific spine types on MSNs of the NAc core and shell were quantified.…”

Translational Assessment of Reward and Motivational Deficits in Psychiatric Disorders

“…After training, anticipatory behavior is assessed on a test day immediately prior to the time of day when the reward is typically presented. Increased locomotor activity has been observed in rodents in anticipation of food (known as food-anticipatory activity) (Mistlberger, 1994), a sweet palatable reward (Hsu et al , 2010; Mendoza et al , 2005), a sexually receptive female (Mendelson and Pfaus, 1989; Pfaus and Phillips, 1991), or a drug reward (i.e., ethanol) (Buck et al , 2014a). While many of the studies on anticipatory pleasure involved rodents, food-anticipatory activity is conserved across species, including honeybees (Moore et al , 1989), fish (Weber and Spieler, 1987), birds (Wenger et al , 1991), rabbits (Jilge, 1992), and monkeys (Sulzman et al , 1977).…”

“…Indeed, increased anticipatory motor behavior was positively correlated with frequency of high ultrasonic vocalizations (Brenes and Schwarting, 2015). High ultrasonic vocalizations were emitted in anticipation of several rewarding stimuli, including food (Buck et al , 2014b; Opiol et al , 2015), a cocaine or ethanol reward (Buck et al , 2014a; Ma et al , 2010), and being reunited with a cage mate after a period of social isolation (Willey and Spear, 2012). As with anticipatory activity, blocking dopamine neurotransmission attenuated high ultrasonic vocalizations in response to food (Buck et al , 2014b).…”

Alcohol enhances unprovoked 22–28kHz USVs and suppresses USV mean frequency in High Alcohol Drinking (HAD-1) male rats

“…USVs have received increased attention in drug abuse studies because administration of cocaine [18], amphetamine [19] and drug-associated cues [20, 21] increase 50–55 kHz frequency-modulated (FM) USV emissions. In addition, escalated levels of alcohol consumed by alcohol-dependent rats are significantly correlated with alcohol anticipatory 50–55 kHz FM USVs [22] and alcohol-dependent rats in a state of withdrawal are more easily provoked to emit negative affect-associated 22–28 kHz USVs by mild aversive stimuli [23, 24]. Ascending mesolimbic cholinergic [25] and dopaminergic pathways [26] mediate production of 22–28 kHz and 50–55 kHz FM USVs, repeatedly, in correspondence with negative and positive emotional states [14, 27, 28].…”