Estrogen‐ and Delay‐Dependent Effects of Δ9‐THC on Memory in Female Rats

Abstract

The cannabinoid receptor agonist, Δ9‐tetrahydrocannabinol (Δ9‐THC), is a psychoactive constituent of marijuana, and has been shown to produce sex‐dependent changes in learning and memory. This study examined the effects of estrogen 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, female rats were trained to respond under a repeated acquisition and delayed‐performance procedure and then ovariectomized. During the acquisition phase of this procedure, rats acquired a 4‐response sequence on three response keys (center, left and right), and sequences changed daily (CRLC, LRCL, RLCR, etc). Sequence acquisition was followed by a delay phase (1 minute to 24 hours), and a delayed‐performance phase in which rats were required to emit the previously acquired sequence. Responding in the acquisition and delayed‐performance phases was maintained under a second‐order fixed‐ratio 3 schedule of food presentation. Δ9‐THC or vehicle (control) was administered 30 minutes prior to the delayed‐performance phase, regardless of delay duration, in order to specifically assess memory, which was quantified by a percent savings measure. Response rate and the percentage of errors were also recorded. To further examine the effects of estrogen, OVX female rats were chronically administered estradiol using a subcutaneous capsule containing a 25/75% ratio of estradiol to cholesterol. The disruptive effects of Δ9‐THC on memory were assessed prior to and during estradiol administration. Prior to estradiol administration, increasing delays ranging from 1 minute to 24 hours produced delay‐dependent decreases in percent savings. When the delay was 1 hour, acute administration of Δ9‐THC produced dose‐dependent decreases in response rate and percent savings, and increases in percent errors, that were significantly attenuated by estradiol administration. Increasing the delay from 1 to 3 hours enhanced the effects of low doses of Δ9‐THC (e.g., 0.56 mg/kg) and produced a significant decrease in percent savings. These results demonstrate the delay‐dependent effects of Δ9‐THC on memory and the involvement of estrogen in modulating Δ9‐THC's acute memory‐disrupting effects in female rats.Support or Funding Information–NIH‐NIDA: R01‐DA037255‐02S1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.