Gender differences in zebrafish responses to cocaine withdrawal

Abstract

The acute responses to cocaine and its withdrawal contribute to cocaine dependence and potentiate relapse, with gender being one of the genetic factors affecting the outcome. Here we report that in both male and female zebrafish (Danio rerio, AB strain), an initial low-dose cocaine treatment (1.5μM, immersion) does not acutely change their behavior. The cocaine withdrawal, however, is associated with an anxiety-like state that develops earlier in female zebrafish but is more robust and persistent in males, and can be acutely attenuated by cocaine administration. This is not a result of gender differences in the expression of anxiety-like state, since behavioral responses to an anxiogenic drug, FG-7142, are similar in male and female zebrafish. The basal brain dopamine (DA) levels and the expression of dopamine transporter mRNA (zDAT) show no significant sexual dimorphism. Acute cocaine exposure does not significantly change DA or zDAT. Withdrawal from repeated cocaine administration results in an overall reduction in zDAT, as well as an increase in DA levels. Neither treatment leads to significant gender differences in brain DA or zDAT. The common and gender-specific effects of cocaine on zebrafish, a well-characterized model of vertebrate development and genetics, should help in understanding the mechanisms involved in the anxiety associated with cocaine withdrawal and provide new opportunities in search for therapeutic solutions.

An integrative analysis of ethanol tolerance and withdrawal in zebrafish (Danio rerio)

“…The increase in dopamine, serotonin, and their metabolites following ethanol withdrawal has also been previously shown [23]. Similar to ethanol, cocaine withdrawal has also been found to induce significant increases in dopamine levels as well as decreases in the expression of the dopamine transporter gene ( zDAT ) [40]. The dopamine transporter is important for the reuptake of dopamine from the synapse [41].…”

Impulsivity as a behavioral measure of withdrawal of orally delivered PCP and nondrug rewards in male and female monkeys

“…Furthermore, in human laboratory studies, glucose tablets decreased tobacco craving that occurred after smoking cessation (West et al 1990) and tobacco craving after overnight abstinence (West et al 1999). Other effects of drug withdrawal have been noted in rats such as increased stress responses during nicotine withdrawal (Jonkman et al 2008), increased anxiogenic effects during ETOH withdrawal (Gatch and Lal 2001;Varlinskaya and Spear 2004) or cocaine withdrawal in zebrafish (LopezPatino et al 2008a) which was later shown to be greater in males than in females (Lopez-Patino et al 2008b). Thus, behaviors that characterize the abstinence or withdrawal phase (impulsivity, motivation, stress, anxiety, reward seeking, and craving) are complex and interrelated.…”

Reducing the Noise in Behavioral Assays: Sex and Age in Adult Zebrafish Locomotion

“…[6][7][8][9] Magguran et al demonstrated that the mating tank itself used in behavioral studies can lead to sex-specific behaviors. 10 In experiments which include the interactions of multiple zebrafish, sex and color 11,12 and age 13,14 have been shown to be determinants of behaviors, including interactions between fish and locomotion.…”