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. Ultrasonic vocalizations (USVs) in rats have been used to measure emotional states, with 50 kHz USVs indicating positive states and 22 kHz USVs indicating negative states. Total and categorized numbers of 22 and 50 kHz USVs and USVs during a visual stimulus (e.g. a potential measure of reinforcement-enhancement) were examined in rats following injection of 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 and 0.4 mg/kg) and PCP (2.0 mg/kg) on three challenge days. PCP acutely decreased 50 kHz vocalizations, whereas 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 with rats in the control groups on challenge days. We conclude that PCP may produce a reward deficit, which is shown by decreased 50 kHz USVs, and behaviors post-PCP exposure may best model the comorbidity between schizophrenia and nicotine.

Figure 1

PCP and SAL group 50 kHz vocalizations (mean+ SEM) by day. The PCP-SAL group emitted fewer 50 kHz vocalizations in comparison to the SAL-SAL group on the first day according to LSD tests * p<0.05, n=7 and n=8 respectively

Figure 2

Effect of nicotine (mean + SEM) on 50 kHz vocalizations over all days of drug testing. The low dose nicotine group emitted more 50 kHz vocalizations than the SAL-SAL group. * p<0.05. SAL-SAL, n=7/group; nicotine, n=8/group.

Figure 3

Effect of PCP (mean ± SEM) on 50 kHz vocalizations emitted during light stimuli, over days of drug testing. The PCP-SAL group made fewer vocalizations than the SAL-SAL group on the first and second day according to LSD tests. * p<0.05.

Figure 4

Effect of nicotine (mean + SEM) on 50 kHz vocalizations emitted during light stimuli over drug testing days. The low dose nicotine group and high dose nicotine group emitted more 50 kHz vocalizations than the SAL-SAL group. * p<0.05.

Figure 5

Differences between groups on the first drug session in subtypes of 50 kHz vocalizations (mean + SEM). SAL-SAL had higher composite and multistep vocalizations than all other groups and groups that had previously received high dose nicotine (0.4 mg/kg) had lower upward ramp vocalizations. ^#p=0.50; * p<0.05. n= 7 or 8/ group.

Figure 6

Examples of vocalizations that look like subtypes of 50 kHz vocalizations but were within the range of 22 kHz vocalizations.

Figure 7

Overall 50 kHz vocalizations (mean + SEM) on the low -dose nicotine challenge day, separated by group. Rats that had previously received any dose of nicotine had higher vocalizations than the SAL-SAL group. * p<0.05

Figure 8

Overall 50 kHz vocalizations (mean + SEM) on the high-dose nicotine challenge day, separated by group. Only rats that had previously received SAL-NIC 0.4 had higher vocalizations than the SAL-SAL group. * p<0.05

Figure 9

Overall 50 kHz vocalizations (mean + SEM) on the PCP challenge day, separated by group. Groups that had previously received both nicotine and PCP (either dose) had higher vocalizations than the SAL-SAL and PCP-SAL groups. * p<0.05