Time-dependent regulation of perineuronal nets in the cerebellar cortex during abstinence of cocaine-self administration.
Psychopharmacology. 2021-01-03; 238(4): 1059-1068
DOI: 10.1007/s00213-020-05752-0
Lire sur PubMed
Sanchez-Hernandez A(1), Nicolas C(2), Gil-Miravet I(1), Guarque-Chabrera J(1), Solinas M(2), Miquel M(3).
Author information:
(1)Área de Psicobiología, Universitat Jaume I, Avenida Vicente Sos Baynat sn,
12071, Castellón de la Plana, Spain.
(2)INSERM, U-1084, Laboratoire de Neurosciences Expérimentales et Cliniques,
Université de Poitiers, Poitiers, France.
(3)Área de Psicobiología, Universitat Jaume I, Avenida Vicente Sos Baynat sn,
12071, Castellón de la Plana, Spain. .
RATIONALE: The probability of structural remodeling in brain circuits may be
modulated by molecules of perineuronal nets (PNNs) that restrict neuronal
plasticity to stabilize circuits. Animal research demonstrates that addictive
drugs can remodel PNNs in different brain regions, including the cerebellum.
OBJECTIVE: This study aimed to investigate the effects of short versus extended
access to cocaine self-administration on PNN expression around Golgi
interneurons in the cerebellar cortex after different periods of abstinence.
METHODS: After 1 week of training (2 h/day), Sprague-Dawley rats
self-administered cocaine daily for 20 days under short (ShA) or extended (LgA)
access. PNN expression in the cerebellum was assessed after 1 day, 7 days, and
28 days of forced abstinence. PNNs were immunolabeled using Wisteria floribunda
agglutinin (WFA) and captured by confocal microscopy.
RESULTS: WFA intensity increased in PNN-bearing Golgi neurons over the
abstinence period and a higher proportion of more intense PNNs were formed
throughout the first month of abstinence. After the first 24 h of cocaine
abstinence, however, we found a reduction in WFA intensity in the cerebellar
cortex of rats with ShA to cocaine as compared to naïve animals. When comparing
with naïve rats, LgA rats showed consistent PNN upregulation at 28 days of
cocaine abstinence.
CONCLUSIONS: Our results suggest that cocaine self-administration produces
modifications in PNN that enhance conditions for synaptic plasticity in the
cerebellar cortex. These modifications are revealed shortly after the cessation
of drug intake but PNNs become more intense during protracted abstinence in the
LgA group, pointing to the stabilization of drug-induced synaptic changes. These
findings indicate that extended access to cocaine self-administration
dynamically regulates conditions for plasticity in the cerebellum during
abstinence.
DOI: 10.1007/s00213-020-05752-0
PMID: 33388819 [Indexed for MEDLINE]