Sex differences in behavioral and PKA cascade responses to repeated cocaine administration
| Autor: | Shirzad Jenab, Karen Weierstall, Wei-Lun Sun, Ana Christina E. Minerly, Jan Weiner, Luyi Zhou, Vanya Quinones-Jenab |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty media_common.quotation_subject medicine.medical_treatment Motor Activity Nucleus accumbens Nucleus Accumbens 03 medical and health sciences Sex Factors 0302 clinical medicine Cocaine Dopamine Uptake Inhibitors Internal medicine medicine Animals Protein kinase A Saline Sensitization media_common Pharmacology Behavior Animal Addiction Cyclin-dependent kinase 5 Phosphotransferases Putamen Cyclin-Dependent Kinase 5 Drug Tolerance Cyclic AMP-Dependent Protein Kinases Rats Sexual dimorphism 030104 developmental biology medicine.anatomical_structure Endocrinology Female Caudate Nucleus Psychology Proto-Oncogene Proteins c-fos Locomotion 030217 neurology & neurosurgery Signal Transduction FOSB |
| Zdroj: | Psychopharmacology. 233:3527-3536 |
| ISSN: | 1432-2072 0033-3158 |
| Popis: | Previous studies have shown sex different patterns in behavioral responses to cocaine. Here, we used between-subject experiment design to study whether sex differences exist in the development of behavioral sensitization and tolerance to repeated cocaine, as well as the role of protein kinase A (PKA) signaling cascade in this process. Ambulatory and rearing responses were recorded in male and female rats after 1 to 14 days of administration of saline or cocaine (15 mg/kg; ip). Correspondent PKA-associated signaling in the nucleus accumbens (NAc) and caudate-putamen (CPu) was measured at each time point. Our results showed that females exhibited higher cocaine-induced behavioral responses and developed behavioral sensitization and tolerance faster than males. Whereas females developed behavioral sensitization to cocaine after 2 days and tolerance after 14 days, male rats developed sensitization after 5 days. In addition, cocaine induced a sexual dimorphic pattern in the progression of neuronal adaptations on the PKA cascade signaling in region (NAc vs. CPu) and time (days of cocaine administration)-dependent manners. In general, more PKA signaling cascade changes were found in the NAc of males on day 5 and in the CPu of females with repeated cocaine injection. In addition, in females, behavioral activities positively correlated with FosB levels in the NAc and CPu and negatively correlated with Cdk5 and p35 in the CPu, while no correlation was observed in males. Our studies suggest that repeated cocaine administration induced different patterns of behavioral and molecular responses in the PKA cascade in male and female rats. |
| Databáze: | OpenAIRE |
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