Endogenous enkephalin is necessary for cocaine-induced alteration in glutamate transmission within the nucleus accumbens

GUZMAN ANDREA SUSANA; CANCELA LILIANA M; GUZMAN ANDREA SUSANA; CANCELA LILIANA M; MONGI-BRAGATO, BETHANIA; GARCIA-KELLER CONSTANZA; MONGI-BRAGATO, BETHANIA; GARCIA-KELLER CONSTANZA; AVALOS MARIA PAULA; BOLLATI FLAVIA; AVALOS MARIA PAULA; BOLLATI FLAVIA

EUROPEAN JOURNAL OF NEUROSCIENCE

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2020

0953-816X

Altered glutamate transmission within the Nucleus Accumbens (NAc) has been proposed as a central mechanism underlying behavioural sensitization associated with repeated cocaine exposure. In addition to glutamate, enkephalin, an endogenous opioid peptide derived from proenkephalin, is necessary for the neuroadaptations associated with chronic cocaine. However, the influence of enkephalin on long-term changes in glutamate transmission within the NAc associated with cocaine-induced sensitization has not been described. This study used knockout proenkephalin mice (KO) to study the influence of endogenous enkephalin on the adaptations in glutamate neurotransmission associated with repeated cocaine treatment. Wild type (WT) and KO mice were treated with daily cocaine injections for 9 days to induce sensitization. On days 15 and 21, the animals received a cocaine challenge and locomotor sensitization was evaluated, and microdialysis was performed to determine accumbens glutamate content on day 21. No expression of behavioural sensitization to cocaine was evidenced in the KO mice. Consistently, these showed no changes in glutamate transmission in the NAc associated with rpeated cocaine. This study reveals a central role of enkephalin in regulating the glutamate mechanisms associated with cocaine sensitization.