Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase

Abstract

Background: In previous studies with male and female rhesus monkeys, withdrawal of access to oral phencyclidine (PCP) self-administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females, and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer impulsive choice for SACC increased during PCP withdrawal more in males than females.

Objectives: The goal of the present study was to examine the effect of PCP (0.25 or 0.5 mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle.

Materials and methods: In component 1, PCP and water were available from two drinking spouts for 1.5 h sessions under concurrent FR 16 schedules. In component 2, a SACC solution was available for 45 min under a DD schedule. Monkeys had a choice of one immediate SACC delivery (0.6 ml) or six delayed SACC deliveries, and the delay was increased by 1 s after a response on the delayed lever and decreased by 1 s after a response on the immediate lever. There was then a 10-day water substitution phase, or PCP withdrawal, that occurred during the mid-follicular phase (days 7-11) or the late luteal phase (days 24-28) of the menstrual cycle. Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases.

Results: PCP deliveries were higher during the luteal (vs follicular) phase. Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration.

Conclusions: PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys.

Fig 1

Mean (±SEM) values are presented for seven female monkeys during the follicular phase (left frames) or luteal phase (right frames) of their menstrual cycle during four experimental conditions: water baseline (Wat –BL) with access only to water for an extended period, PCP access during the follicular (F) or luteal (L) phase) (PCP-F or PCP-L), PCP (0.25 mg/ml) pre-withdrawal (PCP Pre-WD) immediately prior to withdrawal, and during withdrawal when water was substituted for PCP (wat-WD). The first term in the x-axis labels refers to the substance that was available for oral consumption during sessions, and the second term indicates baseline (BL) during the follicular (F) or luteal (L) phase or withdrawal (WD) of PCP. Frames a and b represent water or PCP deliveries earned under component 1 during the follicular and luteal phase of the menstrual cycle, respectively, when liquids were available under independent concurrent FR 8 schedules for 2 h. Frames c and d indicate the number of SACC deliveries, during the follicular (F) or luteal (L) phase, earned during component 2 under a delay-discounting task whereby the monkeys could earn one SACC delivery immediately under FR 8 or 6 deliveries after a delay, with the 1 or 6 deliveries each under an FR 8 schedule. Frames e and f depict the mean adjusted delay (MAD) calculated from the 45 choice trials under DD schedule during the follicular (F) or luteal (L) phase of the menstrual cycle, respectively. Significant differences across experimental conditions are indicated by * (p < 0.05) and ** (p < 0.01), and significant differences between the follicular and luteal phases are indicated by # (p < 0.05), ## (p < 0.01).

Fig 2

Fig 2 is the same as described for Fig 1 except the PCP concentration was 0.5 mg/ml. All other aspects of Fig 2 are as noted in Fig. 1.