The positive reinforcing effects of cocaine and opposite-sex social contact: roles of biological sex and estrus

Abstract

Rationale: Preclinical studies report that drug use and social contact mutually influence the reinforcing effects of one another. Most of these studies have used same-sex dyads exclusively, and the role of factors related to biological sex and hormonal fluctuations are not well understood.

Objectives: The purpose of this study was to examine the reinforcing effects of cocaine and social contact with an opposite-sex partner in male and female rats, and how these effects are modulated by ovarian hormones.

Methods: Male and female rats were trained in a nonexclusive choice procedure in which cocaine and social contact with an opposite-sex partner were simultaneously available on concurrent progressive ratio schedules of reinforcement. To examine the effects of ovarian hormones related to estrous cycling, Experiment 1 used naturally cycling, gonadally intact females, whereas Experiment 2 used ovariectomized females, and estrus was artificially induced with exogenous hormones.

Results: In both experiments, cocaine and social contact functioned as robust reinforcers, and there were no significant effects of biological sex or estrus status of the females. The positive reinforcing effects of both cocaine and social contact increased as a function of cocaine dose, indicating that contingent cocaine administration increases the reinforcing effects of social contact.

Conclusions: These data suggest that cocaine use among opposite-sex partners may enhance factors that contribute to social bonding.

Keywords: Addiction; Animal model; Choice; Concurrent schedule; Estrous cycle; Progressive ratio; Sex differences; Social behavior.

Fig. 1

Timeline of events for Experiments 1 and 2. Created with BioRender.com

Fig. 2

Upper Panels: Breakpoints maintained by cocaine and opposite-sex social contact in female (left: n = 9) and male (right: n = 9) rats under a concurrent PR-PR schedule of reinforcement. Data were collected when females (either responder females or female partners) were in either (1) metestrus or diestrus (met/diestrus), (2) proestrus, (3) during the transition between proestrus and estrus (Pro <--> Est), and (4) estrus. Lower Panels: Data from various stages of the female’s estrous cycle when collapsed into metestrus/diestrus or proestrus/estrus. Horizontal bars represent mean (± SEM). Gray dots represent data from individual subjects

Fig. 3

Breakpoints maintained by cocaine and opposite-sex social contact in female (left: n = 9) and male (right: n = 9) rats from Fig. 2. Data are shown separately for breakpoints maintained by cocaine and opposite-sex social contact to emphasize biological sex comparisons. Horizontal bars represent mean (± SEM). Gray dots represent data from individual subjects

Fig. 4

Cumulative records from the female (R4535: left) and male (R4516: right) rat most consistently representative of the group mean from Experiment 1 when the female (either responder female or female partner) was in metestrus/diestrus (top) or proestrus/estrus (bottom). Left axis depicts cumulative number of responses; bottom axis reflects time (min) in sessions. Cumulative records depict responding maintained by the social (blue) and cocaine (green) reinforcers. Reinforcer delivery noted by triangles

Fig. 5

Breakpoints maintained by cocaine (triangles) and opposite-sex social contact (circles) in ovariectomized female (left: n = 9) and intact male (left: n = 10) rats under a concurrent PR-PR schedule of reinforcement. Left axis depicts breakpoints expressed as number of reinforcers obtained; bottom axis depicts doses of cocaine (or saline) in mg/kg/infusion. Data were collected under control (i.e., non-hormone: open symbols) conditions and under conditions in which estrus was artificially induced by exogenous hormone administration (filled symbols) in females. Data reflect the mean (± SEM)

Fig. 6

Breakpoints maintained by opposite-sex social contact (left) and cocaine (right) in ovariectomized female (n = 9) and intact male (n = 10) rats under a concurrent PR-PR schedule of reinforcement. Data are shown when responding on the cocaine-designated lever was reinforced with saline (SAL), 0.5 mg/kg/infusion cocaine (0.5 Coc), and 1.5 mg/kg/infusion cocaine (1.5 Coc), and when data were collected under control (i.e., non-hormone) conditions and under conditions in which estrus was artificially induced by exogenous hormone administration in females. Horizontal bars represent mean (± SEM). Gray dots represent data from individual subjects. This Fig. is created from the same dataset used for Fig. 5 and depicted to emphasize biological sex comparisons

Fig. 7

Cumulative records from the female (R4834: left columns) and male (R4857: right columns) rat most consistently representative of the group mean from Experiment 2. Data are shown when responding on the cocaine-assigned lever resulted in the delivery of 0.0 (saline: upper panels), 0.5 mg/kg (middle panels), or 1.5 mg/kg cocaine (lower panels). Data are also shown under control conditions (first and third column) and during artificially induced estrus (second and fourth columns). Left axis depicts cumulative number of responses; bottom axis reflects time (min) in sessions). Cumulative records depict responding maintained by the social (blue) and cocaine (green) reinforcers. Reinforcer delivery noted by triangles. All graphs truncated at 600 responses