Effects of the phencyclidine model of schizophrenia and nicotine on total and categorized ultrasonic vocalizations in rats

Abstract

Patients with schizophrenia smoke cigarettes at a higher rate than the general population. We hypothesized that a factor in this comorbidity is sensitivity to the reinforcing and reinforcement-enhancement effects of nicotine. Phencyclidine (PCP) was used to model behavioral changes resembling negative symptoms of schizophrenia in rats. USVs in rats have been used to measure emotional states, with 50 kHz USVs indicating positive states and 22 kHz indicating negative. Total and categorized numbers of 22 and 50 kHz ultrasonic vocalizations (USVs) and USVs during a visual stimulus (e.g. a potential measure of reinforcement-enhancement) were examined in rats following .injection ofh PCP (2.0 mg/kg), and/or nicotine (0.2 or 0.4 mg/kg) daily for 7 days. PCP was then discontinued and all rats received nicotine (0.2 mg/kg and 0.4 mg/kg) and PCP (2.0 mg/kg) on 3 challenge days. PCP acutely decreased 50 kHz vocalizations while repeated nicotine potentiated rates of vocalizations, with similar patterns during light presentations. Rats in the PCP and nicotine combination groups made more 50 kHz vocalizations compared to control groups on challenge days. We conclude that PCP may produce a reward deficit that is shown by decreased 50 kHz USVs, and behaviors post-PCP exposure may best model the comorbidity between schizophrenia and nicotine.

Alterations of acoustic features of 50 kHz vocalizations by nicotine and phencyclidine in rats

“…This study examined the long-term alterations in acoustic features of 50 kHz vocalizations produced by two drugs of abuse, phencyclidine (PCP) and nicotine. In a previous study, we found that chronic but not acute nicotine increased 50 kHz vocalizations, whereas PCP acutely decreased the total number of vocalizations (Swalve et al, 2016). However, the long-term effects of nicotine on features such as bandwidth and maximum frequency as well as the potential significance of these chronic alterations are unknown.…”

“…Pre-injections of nicotine were given to each rat 2 h after each habituation day in their home cages to limit the initial aversive effect of nicotine (Bevins and Besheer, 2001). Vocalizations of these animals had previously been used to examine the interaction of nicotine and PCP on total and categorized vocalizations (Swalve et al, 2016). In this experiment, four groups of rats were examined, divided into groups based on drug administration: SAL, SAL-NIC 0.2 mg/kg (NIC2), SAL-NIC 0.4 mg/kg (NIC4), and PCP.…”

“…All rats were single-housed in clear rectangular polycarbonate tubs (48.3 cm × 26.7 cm × 20.3 cm) after arrival to avoid isolation-induced stress and vocalizations that would occur during the experimental procedures if rats were pair-housed. This dataset was analyzed for a prior experiment (Swalve et al, 2016) but all data reported here are new and have never been reported before. Rats had at least 5 days of habituation to the animal facility with 5 min of handling per day before experimental sessions commenced.…”

“…Myriad psychoactive drugs with addictive and rewarding properties have acutely produced alterations in total 50-kHz USVs as well as specific subtypes of vocalizations, including amphetamine, cocaine, and methylphenidate (Williams and Undieh, 2010;Wright et al, 2010;Simola et al, 2012Simola et al, , 2014, whereas other drugs do not produce differences in total 50 kHz vocalizations. such as morphine, 3,4-methylenedioxymethamphetamine, and nicotine (Wright et al, 2010;Sadananda et al, 2012;Simola et al, 2010;2014;Swalve et al, 2016). Vocalization patterns are also known to change over time, as seen with amphetamine and nicotine (Simola et al, 2014;Swalve et al, 2016).…”

“…such as morphine, 3,4-methylenedioxymethamphetamine, and nicotine (Wright et al, 2010;Sadananda et al, 2012;Simola et al, 2010;2014;Swalve et al, 2016). Vocalization patterns are also known to change over time, as seen with amphetamine and nicotine (Simola et al, 2014;Swalve et al, 2016). Acoustic features of 50 kHz vocalizations such as maximum frequency and bandwidth have recently been identified as a method for further examination of psychoactive substances and may have behavioral significance (Brudzynski, 2005;Simola et al, 2012), potentially encoding such information as magnitude or urgency of the signal, but few studies have examined these features after drug administration (Simola et al, 2012).…”