Related Experiment Video
Updated: May 28, 2026
A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
Role of actin depolymerizing factor in the development of methamphetamine-induced place preference in mice
Masahiro Shibasaki1, Koji Mizuno, Kazuhiro Kurokawa
1Department of Pharmacology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan.
Abstract:
The present study investigated role of actin depolymerizing factor (ADF) in methamphetamine-induced place preference using ADF mutant (ADFm) and wild-type mice (WT). Whereas methamphetamine developed dose-dependently place preference in wild-type mice, methamphetamine-induced place preference was significantly attenuated by ADF mutation. Moreover, the administration of phalloidin, an F-actin stabilizer, dose-dependently inhibited methamphetamine-induced place preference. Methamphetamine-conditioning significantly increased the protein levels of ADF, cofilin, G-actin and F-actin in the limbic forebrain of both WT and ADFm, though the degree of enhancement of G- and F-actins by methamphetamine in ADFm was significantly smaller than in WT. Immunohistochemical study showed the co-localization of synaptophysin and tyrosine hydroxylase in WT and the potentiation of the immunoreactivity of these proteins by methamphetamine-conditioning, whereas such potentiation was suppressed by ADF mutation. In addition, the protein levels of synaptophysin, post-synaptic density 95 (PSD95), and neuroligin1 significantly increased in the limbic forebrain of WT showing methamphetamine-induced place preference, but not in ADFm. These findings indicate that ADF play an important role in the development of methamphetamine-induced place preference via regulation of actin dynamics.
Insights
Actin depolymerizing factor (ADF) is crucial for methamphetamine-induced place preference. Stabilizing F-actin or mutating ADF significantly reduces this drug-seeking behavior, highlighting ADF's role in addiction.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Methamphetamine (METH) is a psychostimulant drug with high abuse potential.
- Actin dynamics, regulated by actin depolymerizing factor (ADF), are implicated in synaptic plasticity and drug addiction.
- The precise role of ADF in METH-induced place preference remains unclear.
Purpose of the Study:
- To investigate the role of actin depolymerizing factor (ADF) in the development of methamphetamine-induced place preference.
- To examine the effects of ADF mutation and F-actin stabilization on METH-induced behavioral responses.
Main Methods:
- Utilized wild-type (WT) and ADF mutant (ADFm) mice to assess METH-induced place preference.
- Administered phalloidin, an F-actin stabilizer, to evaluate its effect on METH-induced place preference.
- Quantified protein levels of ADF, cofilin, G-actin, F-actin, synaptophysin, tyrosine hydroxylase, PSD95, and neuroligin1 in the limbic forebrain via Western blot and immunohistochemistry.
Main Results:
- METH induced dose-dependent place preference in WT mice, which was significantly attenuated in ADFm mice.
- Phalloidin administration dose-dependently inhibited METH-induced place preference.
- METH-conditioning increased ADF, cofilin, G-actin, and F-actin levels in the limbic forebrain, with a smaller increase observed in ADFm mice.
- ADF mutation suppressed the potentiation of synaptophysin and tyrosine hydroxylase immunoreactivity induced by METH-conditioning.
- Protein levels of synaptophysin, PSD95, and neuroligin1 were elevated in WT mice exhibiting METH-induced place preference but not in ADFm mice.
Conclusions:
- ADF plays a critical role in the development of methamphetamine-induced place preference.
- Regulation of actin dynamics by ADF is a key mechanism underlying METH-induced behavioral responses.
- Targeting ADF or actin dynamics may offer novel therapeutic strategies for methamphetamine addiction.
