Interactive Effects of Hormone Status and Δ9‐THC Administration on Memory in Female Rats

Abstract

The cannabinoid receptor agonist, Δ9‐tetrahydrocannabinol (Δ9‐THC), is a psychoactive constituent of marijuana, and a popular recreational drug that has been shown to produce disruptions in learning and memory. Conversely, estrogen has been found to produce a positive effect on learning and memory in female rats. The purpose of this study was to examine the effects of hormone status on memory, and how these effects alter the acute disruptive effects of Δ9‐THC (0.32–3.2 mg/kg) on memory in female rats. To do this, intact and ovariectomized (OVX) female rats were trained on a repeated acquisition and delayed‐performance procedure. During the acquisition phase of this procedure, rats acquired a 4‐response sequence (CRLC, LRCL, RLCR, etc.) that changed daily. Responding was maintained under a second‐order fixed‐ratio 3 schedule of food presentation. Sequence acquisition was followed by a delay phase and a delayed‐performance phase in which rats emitted the previously acquired sequence. Delay phase under baseline conditions was 1 hour. In order to examine the effect of delay, delays ranging from 1 minute to 24 hours were used. Δ9‐THC or vehicle was administered 30 minutes prior to the delayed‐performance phase in order to specifically target retention, which was assessed by percent savings. Response rate and the percentage of errors were also recorded. When the delay was varied under non‐drug conditions, delay‐dependent decreases in percent savings were observed in intact and OVX rats. However, the disruption of retention was greater in OVX than intact rats. Acute administration of Δ9‐THC produced dose‐dependent decreases in response rate and percent savings, and increases in percent errors in both intact and OVX rats under baseline conditions. After administration of 0.56 mg/kg Δ9‐THC, intact rats showed less sequence retention than OVX rats. Increasing the delay to 3 hours produced a leftward shift in the percent‐savings curve for both intact and OVX rats. These results suggest that hormone status directly impacts retention under an acquisition and delayed‐performance procedure, and acute administration of Δ9‐THC produces both delay‐dependent and dose‐dependent effects on memory in intact and OVX female rats.Support or Funding InformationNIH grant R01‐DA037255‐02S1