The goal of the proposed studies is to establish the behavioral correlates of cocaine administration and cocaine withdrawal in zebrafish. The central hypothesis of this proposal is that neurobiological mechanisms of drug reward and drug addiction in lower vertebrates are similar to those in mammals and that investigating them in zebrafish, a lower diurnal vertebrate with well-characterized genetics, would lead to a better understanding of addictive disorders and the development of more effective treatment strategies. This requires a detailed characterization of species-specific responses to cocaine in zebrafish and the evaluation of methodological approaches applicable to large-scale screening procedures. The proposed studies will be accomplished by conducting: i) automatic recordings of zebrafish locomotor activity and conditioned place preference, using digital image analysis system; and ii) high-speed digital imaging of swimming and turning patterns in larval zebrafish. These techniques will allow us to: a) Characterize the effects of cocaine treatment and cocaine withdrawal on locomotor activity and its circadian pattern in larval zebrafish; b) Establish whether zebrafish larvae develops behavioral sensitization to cocaine; c) Determine whether zebrafish larvae develops place preference to cocaine; d) Characterize the effects of cocaine treatment and cocaine withdrawal on specific locomotor patterns, e.g., swimming and turning; e) Determine whether melatonin treatment can modulate cocaine-induced changes in zebrafish behavior. A detailed characterization of the behavioral responses to cocaine in larval zebrafish would create a necessary foundation for intensive studies on the molecular and neuronal mechanisms of drug addiction, using multiple mutant phenotypes and transgenic zebrafish available. This could advance our understanding of the neuronal and intracellular targets of addictive substances and the genetic bases of vulnerability to drug addiction.
| Kacprzak, Victoria; Patel, Neil A; Riley, Elizabeth et al. (2017) Dopaminergic control of anxiety in young and aged zebrafish. Pharmacol Biochem Behav 157:1-8 |
| Riley, Elizabeth; Kopotiyenko, Konstantin; Zhdanova, Irina (2015) Prenatal and acute cocaine exposure affects neural responses and habituation to visual stimuli. Front Neural Circuits 9:41 |
| Zhdanova, Irina V (2011) Sleep and its regulation in zebrafish. Rev Neurosci 22:27-36 |
| Lopez Patino, Marcos A; Yu, Lili; Yamamoto, Bryan K et al. (2008) Gender differences in zebrafish responses to cocaine withdrawal. Physiol Behav 95:36-47 |
| Lopez-Patino, Marcos A; Yu, Lili; Cabral, Howard et al. (2008) Anxiogenic effects of cocaine withdrawal in zebrafish. Physiol Behav 93:160-71 |
| Shang, Eva H; Zhdanova, Irina V (2007) The circadian system is a target and modulator of prenatal cocaine effects. PLoS One 2:e587 |
