A single dose of cocaine raises SV2A density in hippocampus of adolescent rats

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Abstract

Objective: Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane synaptic vesicle glycoprotein 2A (SV2A) of pre-synaptic vesicles is commonly used to measure synaptic density, as a novel approach to the detection of synaptic changes. We do not know if a single dose of cocaine suffices to affect pre-synaptic SV2A density, especially during adolescence when synapses undergo intense maturation. Here, we explored potential changes of pre-synaptic SV2A density in target brain areas associated with the cocaine-induced boost of dopaminergic neurotransmission, specifically testing if the effects would last after the return of dopamine levels to baseline. Methods: We administered cocaine (20 mg/kg i.p.) or saline to rats in early adolescence, tested their activity levels, and removed the brains 1 hour and 7 days after injection. To evaluate immediate and lasting effects, we did autoradiography with [ 3H]UCB-J, a specific tracer for SV2A, in medial prefrontal cortex, striatum, nucleus accumbens, amygdala, and dorsal and ventral areas of hippocampus. We also measured the striatal binding of [ 3H]GBR-12935 to test cocaine's occupancy of the dopamine transporter at both times of study. Results: We found a significant increase of [ 3H]UCB-J binding in the dorsal and ventral sections of hippocampus 7 days after the cocaine administration compared to saline-injected rats, but no differences 1 hour after the injection. The [ 3H]GBR-12935 binding remained unchanged at both times. Conclusion: Cocaine provoked lasting changes of hippocampal synaptic density after a single exposure during adolescence.

Original languageEnglish
JournalActa Neuropsychiatrica
Volume36
Issue2
Pages (from-to)109-117
Number of pages9
ISSN0924-2708
DOIs
Publication statusPublished - Apr 2024

Keywords

  • adolescent
  • autoradiography
  • cocaine
  • neuronal plasticity
  • rats

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