Evaluation of rat ultrasonic vocalizations as predictors of the conditioned aversive effects of drugs.
BACKGROUND
Since cues that predict aversive outcomes can elicit both avoidance and 20 kHz ultrasonic vocalizations (USVs) in adult rats, 20 kHz USVs may also index the conditioned aversive effects of drugs.


OBJECTIVE
We evaluated whether exposure to compartments associated with drugs with aversive effects would selectively increase 20 but not 50 kHz USVs in rats.


METHODS
Rats were injected with naloxone (NAL) or lithium chloride (LiCl) and placed in one compartment or with saline (VEH) and placed in another compartment for three 50-min conditioning sessions. 20 kHz USVs, 50 kHz USVs, and time spent in each chamber were recorded during subsequent 15-min testing sessions during which rats had access to both compartments (expt 1) or were confined to the drug- or VEH-paired compartment (expt 2).


RESULTS
In expt 1, animals conditioned either with NAL (0.3 and 3.0 mg/kg) or LiCl (10 and 30 mg/kg) emitted increased 20 kHz USVs in the drug-paired compartment, relative to VEH-conditioned controls. Conditioning with high doses of both drugs also increased conditioned place aversion and decreased emission of 50 kHz USVs. In expt 2, restriction of animals to the compartment paired with high doses of NAL and LiCl also increased emission of 20 kHz USVs and decreased 50 kHz USVs, relative to VEH-conditioned controls.


CONCLUSIONS
In rats, cues associated with drugs with aversive effects increase 20 kHz USVs and decrease 50 kHz USVs, suggesting that USVs may provide a useful model for predicting the conditioned aversive effects of drugs.
Burgdorf
J
J
Integrative Neuroscience Unit, Behavioral Neuroscience Laboratory, Intramural Research Program, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Knutson
B
B
Panksepp
J
J
Shippenberg
T S
TS
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D003463:Cues; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects* / Q000502:physiology
D000701:Analgesics, Opioid; D018692:Antimanic Agents; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine; D018021:Lithium Chloride