Responding during signaled availability and nonavailability of iv cocaine and food in rats: age and sex differences

Abstract

Rationale: Research suggests that age and sex are vulnerability factors for drug abuse. However, few studies have systematically examined their interaction.

Objective: The purpose of the present study was to examine male and female, adult and adolescent rats under a procedure that measures responding during periods of signaled availability and nonavailability of iv cocaine and food reinforcers.

Methods: Adolescent and adult rats lever pressed for iv infusions of cocaine or food pellets under a procedure with three components of signaled availability of the reinforcer alternating with two components of signaled nonavailability. Adolescent rats were removed and then later retested under the same conditions as adults, and a group of adult rats was also removed and retested after a similar number of days. A subset of rats earning cocaine infusions under the initial test was later retested with food pellets under the same behavioral task to assess the influence of prior cocaine exposure on subsequent responding for a nondrug reinforcer.

Results: Adolescents (vs. adults) made more responses during periods of signaled iv cocaine availability and nonavailabiltiy, and adult females responded more than adult males during these periods. Responding during periods of signaled nonavailability of iv cocaine and food did not differ between the initial and subsequent retest conditions in adult rats. Further, adult males and females exposed to cocaine during adolescence responded more during periods of food availability compared to cocaine-naïve adults.

Conclusion: These results indicate that sex and age are vulnerability factors in cocaine abuse, and cocaine exposure during critical developmental stages can have long-lasting effects.

Fig. 1

Mean (±SEM) responses during signaled availability and nonavailability periods for cocaine-maintained operant sessions. Left panels (a, c, e, and g) depict responding for cocaine under signaled availability, while right panels (b, d, f, and h) depict responses under signaled nonavailability conditions. Panels a–d compare responding maintained cocaine by females and males during adolescence to responses when retested as adults 30 days later. Panels e–h depict responses for adult females and males during initial testing and during a retest 30 days later. Both adolescents and adults responded more during the availability period during the initial test vs. the retest (a, c, e, and g; *p<0.01), and adolescents also responded more during the signaled nonavailability period during the initial test vs. the retest (b and d; *p<0.01). Adolescents responded more during the availability and nonavailability periods than adults during the initial test (a and c vs. e and g and b and d vs f and h; #p<0.01), and among the adults, females responded more than males during both signaled availability and nonavailability periods for both the initial test and retest (e and f vs. g and h; †p<0.05). Adults with adolescent cocaine exposure made more cocaine-reinforced responses than rats that received initial cocaine exposure as adults (a and c vs e and g; @p<0.01)

Fig. 2

Representative cumulative records of responses (vertical steps) and infusions (downward deflections) during cocaine-maintained operant sessions for adolescents (upper panels) and adults (lower panels) during the initial test and retest

Fig. 3

Mean (±SEM) responses during the signaled availability and nonavailability periods for food-maintained operant sessions. Left panels (a, c, e, and g) depict responding for food under signaled availability conditions, while right panels (b, d, f, and h) depict responses under signaled nonavailability conditions. Panels a–d compare responding maintained by food for females and males during adolescence to responses when retested as adults 30 days later. Panels e–h depict responses for adult females and males during initial testing and during a retest 30 days later. Males responded more during the signaled availability period when retested as adults vs. their initial test as adolescents (c; *p<0.05) and also responded more during the signaled availability and nonavailability periods than females retested as adults (c and d vs. a and b; †p<0.01)

Fig. 4

Mean (±SEM) responses during the signaled availability and nonavailability periods for food-maintained operant sessions. Left panels (a, c, e, and g) depict responding maintained by food under signaled availability conditions, while right panels (b, d, f, and h) depict responses under signaled nonavailability conditions. Panels a–d compare responding for food pellets between groups of adult rats that earned cocaine or food pellets (cocaine-naïve) during adolescence. Panels e–h compare responding between groups of adult rats that earned cocaine or food pellets (cocaine-naïve) earlier in adulthood. The cocaine-naïve groups are the same as the food retest groups in Fig. 3 and are renamed. Adult females and males exposed to cocaine during adolescence responded more for food during the signaled availability period than cocaine-naïve adult females and males (a and c; *p<0.05). Further, males, whether cocaine-naïve or cocaine-exposed during adolescence or adulthood, responded more than females during the signaled availability period (c and g vs. a and e; †p<0.05). Adult female and male rats with adolescent cocaine exposure make more reinforced responses than females and males that were exposed to cocaine as adults (a and c vs. e and g; @p<0.05)

Fig. 5

Representative cumulative records of responses (vertical steps) and infusions (downward deflections) during food-maintained operant sessions for adults with previous cocaine exposure during adolescence (upper panels) or adulthood (lower panels)

Fig. 6

Mean (±SEM) saccharin preference scores at 0.03%, 0.10%, 0.30%, and 0.60% (w/v) saccharin solutions for both females and males. Females had significantly higher saccharin preference scores than males at the 0.10%, 0.30%, and 0.60% saccharin concentrations (*p<0.01)