Estradiol administration to ovariectomized rats potentiates mephedrone‐induced disruptions of nonspatial learning

Abstract

Mephedrone (4-methylmethcathinone) has been found in several over-the-counter products that are abused by humans, but very little is known about its behavioral effects and abuse liability. The present study examined the effects of mephedrone (1-10 mg/kg) on learning in female rats, as well as its interaction with the ovarian hormone estradiol. More specifically, female rats were trained to respond under a multiple schedule of repeated acquisition and performance of response sequences and then ovariectomized. Following ovariectomy, mephedrone dose-effect curves were obtained during periods of 17β-estradiol administration and periods without estradiol administration. Unlike mephedrone, which was administered acutely (i.p.) before the experimental sessions, 17β-estradiol was administered via subcutaneous Silastic capsules containing 25% 17β-estradiol and 75% cholesterol. In general, mephedrone produced dose-dependent rate-decreasing and error-increasing effects in the acquisition and performance components of the schedule in all subjects. However, when estradiol was present, three of the four rats were more sensitive to the rate-decreasing effects of mephedrone, and all of the subjects were more sensitive to its error-increasing effects. These data indicate that estradiol can potentiate the disruptive effects of mephedrone on both the acquisition and performance of complex behavior in female rats.

Cognitive deficits and neurotoxicity induced by synthetic cathinones: is there a role for neuroinflammation?

“…to rhesus monkeys increased performance in the visuospatial component of a stimulus-associative memory task (Wright et al 2012), consistent with the psychomotor performance-enhancing effects of amphetamine-type psychostimulants (Wood et al 2014). On the other hand, mephedrone-induced disruptions in operant conditioning task performance in ovariectomized female rats has been shown to be potentiated by administration of 17-βestradiol (Weed et al 2014), suggesting that cognition-impairing effects of synthetic cathinones may be influenced by ovarian hormones. Yet as shown in Table 2, synthetic cathinone-induced deficits in cognition have been observed in animals of both sexes.…”

Vulnerability factors for mephedrone-induced conditioned place preference in rats—the impact of sex differences, social-conditioning and stress

“…Hormonal changes in females could be at least one of the possible causes of the observed distinction; however, the relationship between mephedrone effects and ovarian hormones has not been investigated yet. So far, it has been reported that estradiol can potentiate mephedrone-induced disruption in spatial memory in ovariectomized rats (Weed et al 2014 ) and that mephedrone exposure during the gestational period impaired learning and memory in mice offspring through hippocampal damage (Naseri et al 2018 ). Nevertheless, previous studies of other drugs of abuse showed that ovariectomized and castrated rats show different rates of acquisition of cocaine self-administration (Hu et al 2004 ), suggesting that sex hormones may not be crucial for differences in the effect of drugs in female and male rodents.…”

Mechanism of psychoactive substance-induced cognitive disorders: does tau protein play a role?

“…Besides, MDPV caused widespread disruption of brain functional connectivity in rats which is linked to cognitive functions [204]. Several other studies in rodents also reported the CDs caused by synthetic cathinones [205][206][207][208][209].…”