ABSTRACT
RATIONALE: Adult rat 22- and 50-kHz ultrasonic vocalizations (USVs) are commonly considered as indices of negative and positive affect, respectively. More specifically, we have proposed that positive affective states are revealed by a predominance of trill over flat 50-kHz call subtypes. However, the 50-kHz call subtypes emitted during aversive drug states remain largely uninvestigated. OBJECTIVES: To determine whether acute morphine withdrawal affects 50-kHz call rates or alters the relative prevalence of trill and flat calls. METHODS: In experiment 1, adult male rats were given saline or morphine (6 mg/kg SC), then acutely challenged 4 h later with saline or naloxone (1 mg/kg SC), and recorded 10-30 min post-injection. In experiments 2 and 3, rats received saline or morphine (6 mg/kg), followed 4 h later by acute saline or naloxone (0.1 mg/kg) challenge; USVs were subsequently recorded during 30-min place conditioning sessions. RESULTS: Naloxone (0.1 mg/kg) produced a strong conditioned place aversion only after acute morphine pretreatment, consistent with antagonist-precipitated morphine withdrawal. The morphine-naloxone combination decreased the relative prevalence of trills and promoted flat calls. Naloxone given alone (0.1 and 1 mg/kg) inhibited trill calls but did not significantly alter the prevalence of flat calls, whereas morphine given alone (4 h pre-session) was largely without effect. Fifty-kHz call rates were inhibited by naloxone given alone, but otherwise unaffected. Twenty-two-kHz calls were sparse. CONCLUSIONS: The 50-kHz call subtype shift seen during antagonist-precipitated morphine withdrawal was opposite in direction to that previously associated with rewards, and hence may reveal negative affect.
Subject(s)
Analgesics, Opioid/adverse effects , Morphine/adverse effects , Substance Withdrawal Syndrome/drug therapy , Substance Withdrawal Syndrome/psychology , Ultrasonic Waves , Vocalization, Animal/drug effects , Animals , Conditioning, Operant/drug effects , Conditioning, Operant/physiology , Male , Naloxone/pharmacology , Naloxone/therapeutic use , Narcotic Antagonists/pharmacology , Narcotic Antagonists/therapeutic use , Random Allocation , Rats , Rats, Long-Evans , Reward , Vocalization, Animal/physiologyABSTRACT
RATIONALE: Adult rat 50-kHz vocalizations have been proposed to indicate a positive affective state, putatively revealed by a predominance of trill calls over flat calls. However, short-term exposure to non-sedative doses of the euphorigen morphine suppresses calling, with no discernible shift in trill or flat call prevalence. OBJECTIVES: This study aimed to determine whether morphine acutely increases 50-kHz call rates or alters the relative prevalence of trill or flat calls, after long-term morphine exposure or acute pharmacological pretreatment. METHODS: Experiment 1 comprised 10 once-daily tests, alternating between saline and morphine, 1 mg/kg SC, followed by dose-response testing (0, 0.3, 1, and 3 mg/kg). Experiment 2 was similar but included additional testing with morphine in combination with the antinausea drug ondansetron or the peripheral opioid antagonist methylnaltrexone. In experiment 3, morphine was again combined with ondansetron or methylnaltrexone but in rats that were initially drug naïve. RESULTS: In animals that were initially drug naïve, morphine tended to suppress calling and did not alter the 50-kHz call subtype profile. In morphine-experienced rats, morphine acutely increased the 50-kHz call rate and promoted trills over flat calls; short calls were also inhibited. Neither ondansetron nor methylnaltrexone detectably altered any effect of morphine on calling, nor did these two drugs affect 50-kHz calling when given alone. CONCLUSIONS: With chronic exposure, morphine acutely enhances 50-kHz calling and differentially promotes trill calls, mainly at the expense of flat calls. These effects appear consistent with a positive affect interpretation of 50-kHz vocalizations.
