How various drugs affect anxiety‐related behavior in male and female rats prenatally exposed to methamphetamine

Abstract

Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the drugs.

Review of Long-Term Consequences of Maternal Methamphetamine Exposure

“…Our studies demonstrated that increased susceptibility to MA and amphetamine (Macúchová et al 2016(Macúchová et al , Šlamberová et al 2011 after prenatal administration of MA using the Laboras test and the open arena test, both of which showed increased locomotor and exploratory activity after exposure. In females, crosssensitization was also found after acute administration of MDMA and cocaine (Šlamberová et al 2013), suggesting sex differences relative to acute drug administration.…”

Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective

“…Furthermore, animal studies typically involve un-signaled, non-contingent cannabinoid administration by the experimenter, which is presumably stressful compared to self-administration, the mode of cannabinoid intake by humans seeking to reduce anxiety/ stress. We found only one published study that included a comparison of cannabinoid effects on anxiety-like behavior in adult (PND60 or older) male vs female rats: on the elevated plus-maze, a moderate dose of THC (2 mg/kg) increased closed arm time and decreased stretch-attend postures (peering out to open arms from closed arms) in female but not male rats, suggesting increased anxiety-like behavior in females only (Macúchová et al, 2016). Several studies have examined acute cannabinoid effects on anxietylike behavior in adolescent female vs male rats, with variable results: for example, the synthetic cannabinoid CP55,940 was more potent in PND44 females than males in increasing anxiety-like behavior on the elevated plus-maze (Marco et al, 2006), whereas 2 mg/kg THC was anxiolytic in both sexes tested on PND35 (Harte-Hargrove and Dow-Edwards, 2012).…”

Prenatal exposure to modafinil alters behavioural response to methamphetamine in adult male mice

“…Preclinical studies have shown analogous results, i.e. poor pregnancy results such as development of neonatal reflexes (McDonnell‐Dowling and Kelly, 2015a) after oral or subcutaneous administration (McDonnell‐Dowling and Kelly, 2016), memory impairment (Fialova et al, 2015; Macuchova et al, 2014; Slamberova et al, 2014) and increased anxiety in the adult offspring as assessed by different behavioural tests (Macuchova et al, 2016; Slamberova et al, 2015). In a similarly designed study a challenge dose of methamphetamine in adulthood in animals prenatally exposed to the same drug led to higher epileptiform neuronal activity in female rats (Matejovska et al, 2014).…”