Assessment of Ultrasonic Vocalizations During Drug Self-administration in Rats

Abstract

Drug self-administration procedures are commonly used to study behavioral and neurochemical changes associated with human drug abuse, addiction and relapse. Various types of behavioral activity are commonly utilized as measures of drug motivation in animals. However, a crucial component of drug abuse relapse in abstinent cocaine users is "drug craving", which is difficult to model in animals, as it often occurs in the absence of overt behaviors. Yet, it is possible that a class of ultrasonic vocalizations (USVs) in rats may be a useful marker for affective responses to drug administration, drug anticipation and even drug craving. Rats vocalize in ultrasonic frequencies that serve as a communicatory function and express subjective emotional states. Several studies have shown that different call frequency ranges are associated with negative and positive emotional states. For instance, high frequency calls ("50-kHz") are associated with positive affect, whereas low frequency calls ("22-kHz") represent a negative emotional state. This article describes a procedure to assess rat USVs associated with daily cocaine self-administration. For this procedure, we utilized standard single-lever operant chambers housed within sound-attenuating boxes for cocaine self-administration sessions and utilized ultrasonic microphones, multi-channel recording hardware and specialized software programs to detect and analyze USVs. USVs measurements reflect emotionality of rats before, during and after drug availability and can be correlated with commonly assessed drug selfadministration behavioral data such lever responses, inter-response intervals and locomotor activity. Since USVs can be assessed during intervals prior to drug availability (e.g., anticipatory USVs) and during drug extinction trials, changes in affect associated with drug anticipation and drug abstinence can also be determined. In addition, determining USV changes over the course of short-and long-term drug exposure can provide a more detailed interpretation of drug exposure effects on affective functioning. Video LinkThe video component of this article can be found at https://www.jove.com/video/2041/ Protocol *= important points 1. Well-handled male Sprague-Dawley rats are trained to lever press with food reward (45 mg sucrose pellets; Bio-Serv, Frenchtown, NJ). 2. *Intravenous catheters are constructed out of stainless steel cannula (Plastics One, VA) and Silastic tubing. Rats undergo a jugular catheterization surgical procedure to allow drug self-administration. After surgery, catheter patency is maintained by daily flushing with 0.1 ml of a 0.9% saline, heparin and Timentin solution. 3. Cocaine (NIDA Drug Inventory and Supply and Control Program; RTI International, Research Triangle Park, NC) used in this experiment was dissolved in isotonic saline solution (0.9%) in the appropriate dose concentrations according to animal weights (0.75 mg/kg/injection) so that each injection was 0.1 ml. Control animals received saline solution in the same volume/injection. 4...

Specific 50-kHz vocalizations are tightly linked to particular types of behavior in juvenile rats anticipating play

“…The relationship between calls and movement in this case might arise not because the locomotion is causally producing the calls, but because both locomotion and calling are indicative of elevated positive affective. This explanation is consistent with the effects of amphetamine and cocaine, which elicit robust increases in 50-kHz vocalizations and activity levels [ 50 , 51 ], with high frequencies of calls being emitted whether the rats are moving or not [ 52 ]. On the other hand, the affective communication hypothesis offers no explanation for the specific relationships between calls and actions shown in Fig 3 .…”

Non-pharmacological factors that determine drug use and addiction

“…We used ultrasonic vocalizations (USVs) in the range of 50 kHz to investigate the affective response to heroin and cocaine in the rat. It has been reported that rats emit 50-kHz USVs when exposed to natural rewarding stimuli (White et al 1990;Knutson et al 1998;Panksepp and Burgdorf 2000;Burgdorf et al 2000) as well as to addictive drugs (Knutson et al 1999;Maier et al 2010). Consistent with the arousal state mismatch hypothesis, we found that at home, rats emit more 50-kHz USVs when self-administering heroine than when self-administering cocaine (Fig.…”

Social play behavior, ultrasonic vocalizations and their modulation by morphine and amphetamine in Wistar and Sprague-Dawley rats

“…In line with this hypothesis, it has been shown that a dissociation exists between the emission of 50-kHz USVs and behavioral measures of affective responses during drug self-administration or anticipation. Thus, while 50-kHz USVs can be elicited by administration of psychostimulant drugs (Barker et al 2010;Browning et al 2011;Burgdorf et al 2000;Burgdorf and Panksepp 2006;Knutson et al 1998;Maier et al 2010;Simola et al 2012;Thompson et al 2006;Trezza et al 2010;Wintink and Brudzynski 2001), rewarding doses of morphine, MDMA, and nicotine have been related to no changes or even decreases in 50-kHz USV emission (Hamed et al 2012;Sadananda et al 2012;Simola et al 2012;Wright et al 2012).…”