TY - JOUR
T1 - A single dose of cocaine raises SV2A density in hippocampus of adolescent rats
AU - Rossi, Rachele
AU - Bærentzen, Simone Larsen
AU - Thomsen, Majken
AU - Real, Caroline C
AU - Wegener, Gregers
AU - Grassi-Oliveira, Rodrigo
AU - Gjedde, Albert
AU - Landau, Anne
PY - 2024/4
Y1 - 2024/4
N2 - 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 SV2A density after a single exposure during adolescence.
AB - 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 SV2A density after a single exposure during adolescence.
KW - adolescent
KW - autoradiography
KW - cocaine
KW - neuronal plasticity
KW - rats
KW - synaptic vesicle glycoprotein 2A (SV2A)
KW - Rats
KW - Amygdala/drug effects
KW - Positron-Emission Tomography
KW - Cocaine/metabolism
KW - Nerve Tissue Proteins/drug effects
KW - Animals
KW - Corpus Striatum
KW - Hippocampus/drug effects
KW - Membrane Glycoproteins/drug effects
KW - Brain/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85149945229&partnerID=8YFLogxK
U2 - 10.1017/neu.2023.14
DO - 10.1017/neu.2023.14
M3 - Journal article
C2 - 36847240
SN - 0924-2708
VL - 36
SP - 109
EP - 117
JO - Acta Neuropsychiatrica
JF - Acta Neuropsychiatrica
IS - 2
ER -