Cocaine sensitization increases kyphosis and modulates neural activity in adult nulliparous rats

Abstract

Although data from both animals and humans suggests that adult cocaine use can have long term effects on behavior, it is unknown if prior cocaine use affects future maternal behavior in nulliparous females. In the current study, cocaine or saline was administered to adult female rats for 10 days, the animals were withdrawn from cocaine for 7 days, and the females were then exposed to donor pups to induce the expression of maternal behavior. Nulliparous females sensitized to cocaine were more likely to retrieve pups, spent more time caring for the pups, and were more likely to express full maternal behavior on day 8 of pup exposure. The fMRI data revealed significant effects of pup exposure in the hippocampal CA1 region, and effects of cocaine in the anterior thalamus and periaqueductal gray. Prior adult cocaine use may have lasting effects on offspring care, and this effect is not dependent on pup mediated effects or the endocrine changes of gestation and lactation. The present findings provide support for the hypothesis that maternal motivation to exhibit maternal behavior is enhanced by prior cocaine sensitization, possibly due to cross sensitization between cocaine and the natural reward of maternal behavior.

Keywords: cocaine; crouching; hippocampus; kyphosis; maternal behavior; nursing; periaqueductal gray; sensitization; thalamus.

Figure 1

Mean ± SEM number of horizontal beam breaks in 5 min bins on day 1 and day 10 during 90 min activity trials. Saline (SAL n = 8) or 15 mg/kg cocaine (COC n = 9) injection were given IP at 30 min. * Indicates a significant difference between COC day 1 and COC day 10 (p < 0.05).

Figure 2

Percentage of saline and cocaine treated nulliparous rats that maternally responded to the presentation of foster pups over 8 days of continuous pup exposure. * Indicates a significant difference between saline and cocaine treated rats (p < 0.05).

Figure 3

Mean ± SEM seconds (s) duration (A) and frequency (B) for four behaviors during a 15 min maternal care test on the 8th day of pup exposure in nulliparous rats previously treated with 10 consecutive days of saline or 15 mg/kg cocaine as adults. Samples sizes listed in parentheses. * Indicates a significant difference between saline and cocaine for an individual behavior (p < 0.05).

Figure 4

Composite activation maps showing areas of increased BOLD activation in rats presented with an empty presentation stage, stage with pups, and pups in the presence of a male intruder rat. Data are shown for control and cocaine treated rats on day 2 following initial exposure to pups and on day 8 after repeated sessions of exposure in their home cage. Color scale hue indicates percent change in signal intensity. Regions of interest are indicated to the left.

Figure 5

Median activated voxels in the PAG of saline and cocaine treated females presented with an empty stage, stage with pups, and pups with a male intruder rat on days 2 and 8 of pup sensitization (A), and composite activation maps showing areas of increased BOLD activation in rats presented with stage, stage with pups and pups and male intruder (B). Insets at the bottom highlight the area of the periaqueductal grey. Data are shown for control and cocaine treated rats on day 2 following initial exposure to pups and on day 8 after repeated sessions of exposure in their home cage. Color scale hue indicates percent change in signal intensity.