Cocaine self-administration abolishes endocannabinoid-mediated long-term depression of glutamatergic synapses in the ventral tegmental area.
Eur J Neurosci
; 52(11): 4517-4524, 2020 12.
Article
en En
| MEDLINE
| ID: mdl-32959420
ABSTRACT
Drugs of abuse, including cocaine, alter the mechanisms underpinning synaptic plasticity, including long-term potentiation of glutamatergic synapses in the mesolimbic system. These effects are thought to underlie addictive behaviors. In the ventral tegmental area (VTA), glutamatergic synapses also exhibit long-term depression (LTD), a type of plasticity that weakens synaptic strength. This form of synaptic plasticity is induced by low-frequency stimulation and mediated by endocannabinoid (eCB) signaling, which also modulates addictive behaviors. However, it remains unknown whether eCB-LTD in the VTA could be altered by cocaine use. Therefore, the goal of the present study was to examine the impact of cocaine self-administration on eCB-LTD of glutamatergic synapses onto VTA dopaminergic (DA) neurons. To that end, male rats underwent cocaine (0.75 mg/kg/infusion) or saline self-administration under the fixed ratio 1 schedule for 6-9 days. One day after the last self-administration session, the magnitude of eCB-LTD was examined using ex vivo whole-cell recordings of putative VTA DA neurons from naïve rats and rats with saline or cocaine self-administration. The results revealed that cocaine self-administration abolished eCB-LTD. The cocaine-induced blockade of eCB-LTD in the VTA was mediated by an impaired function of presynaptic CB1 receptors. Collectively, these findings indicate that cocaine exposure blunts eCB-mediated synaptic plasticity in midbrain DA neurons. This effect could be one of the cellular mechanisms that mediate, at least in part, addictive behaviors.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cocaína
/
Área Tegmental Ventral
Límite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Asunto de la revista:
NEUROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos