» Articles » PMID: 29234834

Contributions of Prolonged Contingent and Non-contingent Cocaine Exposure to Escalation of Cocaine Intake and Glutamatergic Gene Expression

Overview
Specialty Pharmacology
Date 2017 Dec 14
PMID 29234834
Citations 11
Authors
Affiliations
Soon will be listed here.
Abstract

Similar to the pattern observed in people with substance abuse disorders, laboratory animals will exhibit escalation of cocaine intake when the drug is available over prolonged periods of time. Here, we investigated the contribution of behavioral contingency of cocaine administration on escalation of cocaine intake and gene expression in the dorsal medial prefrontal cortex (dmPFC) in adult male rats. Rats were allowed to self-administer intravenous cocaine (0.25 mg/infusion) under either limited cocaine-(1 h/day), prolonged cocaine-(6 h/day), or limited cocaine-(1 h/day) plus yoked cocaine-access (5 h/day); a control group received access to saline (1 h/day). One day after the final self-administration session, the rats were euthanized and the dmPFC was removed for quantification of mRNA expression of critical glutamatergic signaling genes, Homer2, Grin1, and Dlg4, as these genes and brain region have been previously implicated in addiction, learning, and memory. All groups with cocaine-access showed escalated cocaine intake during the first 10 min of each daily session, and within the first 1 h of cocaine administration. Additionally, the limited-access + yoked group exhibited more non-reinforced lever responses during self-administration sessions than the other groups tested. Lastly, Homer2, Grin1, and Dlg4 mRNA were impacted by both duration and mode of cocaine exposure. Only prolonged-access rats exhibited increases in mRNA expression for Homer2, Grin1, and Dlg4 mRNA. Taken together, these findings indicate that both contingent and non-contingent "excessive" cocaine exposure supports escalation behavior, but the behavioral contingency of cocaine-access has distinct effects on the patterning of operant responsiveness and changes in mRNA expression.

Citing Articles

Transcriptional Profile of Exercise-Induced Protection Against Relapse to Cocaine Seeking in a Rat Model.

Towers E, Shapiro D, Abel J, Bakhti-Suroosh A, Kupkova K, Auble D Biol Psychiatry Glob Open Sci. 2023; 3(4):734-745.

PMID: 37881559 PMC: 10593899. DOI: 10.1016/j.bpsgos.2023.01.007.


Reduced Expression of the Htr2a, Grin1, and Bdnf Genes and Cognitive Inflexibility in a Model of High Compulsive Rats.

Prados-Pardo A, Martin-Gonzalez E, Mora S, Martin C, Olmedo-Cordoba M, Perez-Fernandez C Mol Neurobiol. 2023; 60(12):6975-6991.

PMID: 37523044 DOI: 10.1007/s12035-023-03506-5.


Cocaine self-administration augments kappa opioid receptor system-mediated inhibition of dopamine activity in the mesolimbic dopamine system.

Estave P, Sun H, Peck E, Holleran K, Chen R, Jones S IBRO Neurosci Rep. 2023; 14:129-137.

PMID: 36748012 PMC: 9898071. DOI: 10.1016/j.ibneur.2023.01.004.


Disrupted Decision-Making: EcoHIV Inoculation in Cocaine Dependent Rats.

McLaurin K, Li H, Mactutus C, Harrod S, Booze R Int J Mol Sci. 2022; 23(16).

PMID: 36012364 PMC: 9409394. DOI: 10.3390/ijms23169100.


Cocaine experience induces functional adaptations in astrocytes: Implications for synaptic plasticity in the nucleus accumbens shell.

ODonovan B, Neugornet A, Neogi R, Xia M, Ortinski P Addict Biol. 2021; 26(6):e13042.

PMID: 33864336 PMC: 9446435. DOI: 10.1111/adb.13042.


References
1.
Knackstedt L, Kalivas P . Extended access to cocaine self-administration enhances drug-primed reinstatement but not behavioral sensitization. J Pharmacol Exp Ther. 2007; 322(3):1103-9. DOI: 10.1124/jpet.107.122861. View

2.
Ahmed S, Koob G . Transition from moderate to excessive drug intake: change in hedonic set point. Science. 1998; 282(5387):298-300. DOI: 10.1126/science.282.5387.298. View

3.
Ghasemzadeh M, Vasudevan P, Mueller C . Locomotor sensitization to cocaine is associated with distinct pattern of glutamate receptor trafficking to the postsynaptic density in prefrontal cortex: early versus late withdrawal effects. Pharmacol Biochem Behav. 2009; 92(3):383-92. DOI: 10.1016/j.pbb.2008.12.004. View

4.
Kalivas P, Volkow N, Seamans J . Unmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission. Neuron. 2005; 45(5):647-50. DOI: 10.1016/j.neuron.2005.02.005. View

5.
Yao W, Gainetdinov R, Arbuckle M, Sotnikova T, Cyr M, Beaulieu J . Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity. Neuron. 2004; 41(4):625-38. DOI: 10.1016/s0896-6273(04)00048-0. View