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. 2016 Sep;233(17):3201-10.
doi: 10.1007/s00213-016-4368-9. Epub 2016 Jul 2.

The Effects of Sex, Estrous Cycle, and Social Contact on Cocaine and Heroin Self-Administration in Rats

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Free PMC article

The Effects of Sex, Estrous Cycle, and Social Contact on Cocaine and Heroin Self-Administration in Rats

Ryan T Lacy et al. Psychopharmacology (Berl). .
Free PMC article

Abstract

Rationale: Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts.

Objective: The objective of this study was to examine the role of sex and estrous cycle in a rat model during cocaine and heroin self-administration with male-female and female-female social dyads.

Methods: Male and female virgin rats were trained to self-administer cocaine and heroin in operant conditioning chambers that permitted two rats to self-administer concurrently, but prevented physical contact. Experiment 1 examined cocaine self-administration on a progressive ratio schedule in male-female dyads. Experiments 2 and 3 examined heroin self-administration on a fixed ratio schedule in male-female dyads at constant and varying doses, respectively. Experiment 4 examined heroin self-administration in female-female dyads on a fixed ratio schedule.

Results: Cocaine-maintained breakpoints increased by ∼17 % in females during estrus, but remained consistent in males. Heroin self-administration decreased by ∼70 % during proestrus in females whether they were isolated, housed with males, or housed with females. Heroin self-administration was lower in males than females under some conditions and was not consistently associated with the responding of females.

Conclusions: Cocaine and heroin self-administration is influenced by the estrous cycle in females when in the presence of a male partner. As a novel finding, these data illustrate that heroin self-administration is reduced in females during proestrus regardless of the social context tested. Finally, these data suggest that drug self-administration in males is only minimally influenced by the hormonal status of a female partner.

Keywords: Cocaine; Estrous; Heroin; Self-administration; Sex; Social.

Conflict of interest statement

The authors report no financial conflicts of interest.

Figures

Fig. 1
Fig. 1
Mean cocaine-maintained breakpoints (0.5 mg/kg cocaine) for females (left; n=12) and males (right; n=12) as a function of the female’s estrous cycle. Females reached significantly higher breakpoints during the estrus (E) phase relative to other phases. Male partners did not differ across the estrous cycle of their female partner (*<.05; **<.01).
Fig. 2
Fig. 2
Mean heroin infusions for females (left; n=6) and males (right; n=6) at a constant dose of 0.0075 mg/kg/infusion. Females showed significantly lower heroin self-administration during the proestrus (P) phase of the estrous cycle. Males; however, did not show any differences in heroin infusions as a function of their female partner’s estrous cycle (**<.01).
Fig. 3
Fig. 3
Scatterplot of the data from Experiment 2. Unique symbols represent each rat, the symbols of female (n=6) and male (n=6) partners match (across the figures) indicating a social dyad in the experiment. Data represent self-administration from 5–8 complete estrous cycles.
Fig. 4
Fig. 4
Mean heroin infusions across a range of heroin doses for females (left; n=5) and males (right; n=5) presented as a function of estrus cycle. The data points represent the average number of infusions based on one data point per animal at a given dose and phase of estrous. Results from females indicate a reduction in heroin self-administration during proestrus (P) compared to meta/diestrus (M/D) and estrus (E). Males show reductions in heroin self-administration during the estrus (E) and proestrus (P) phases of their female partners compared to meta/diestrus (M/D). Please note difference in Y-axis between females and males.
Fig. 5
Fig. 5
Area under the curve values derived from the heroin dose-response curve in Experiment 3. Data were calculated using the trapezoidal rule. Females (n=5) show significant reductions during proestrus (P) compared to other phases. Males (n=5) had significantly lower values during both proestrus (P) and estrus (E) compared to meta/diestrus (M/D) of their female partners (*<.05; **<.01). Please note difference in Y-axis between males and females.
Fig. 6
Fig. 6
Mean heroin infusions obtained from female-female dyads (n=12). The mean number of infusions during proestrus (P) was significantly lower than during estrus (E) and meta/diestrus (M/D; *<.05; **<.01).
Fig. 7
Fig. 7
Data obtained from three isolated female rats (R2737, R2779, and R2776) presented as scatterplots. The mean number of infusions was significantly lower during proestrus than during estrus and meta/diestrus.

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