Alcohol-Preferring P Rats Exhibit Elevated Motor Impulsivity Concomitant with Operant Responding And Self-Administration of Alcohol
Overview
Affiliations
Background: Increased levels of impulsivity are associated with increased illicit drug use and alcoholism. Previous research in our laboratory has shown that increased levels of delay discounting (a decision-making form of impulsivity) are related to appetitive processes governing alcohol self-administration as opposed to purely consummatory processes. Specifically, the high-seeking/high-drinking alcohol-preferring P rats showed increased delay discounting compared to nonselected Long Evans rats (LE) whereas the high-drinking/moderate-seeking HAD2 rats did not. The P rats also displayed a perseverative pattern of behavior such that during operant alcohol self-administration they exhibited greater resistance to extinction.
Methods: One explanation for the previous findings is that P rats have a deficit in response inhibition. This study followed up on this possibility by utilizing a countermanding paradigm (stop signal reaction time [SSRT] task) followed by operant self-administration of alcohol across increasing fixed ratio requirements (FR; 1, 2, 5, 10, and 15 responses). In separate animals, 24-hour access 2-bottle choice (10% EtOH vs. water) drinking was assessed.
Results: In the SSRT task, P rats exhibited an increased SSRT compared to both LE and HAD2 rats indicating a decrease in behavioral inhibition in the P rats. Also, P rats showed increased operant self-administration across all FRs and the greatest increase in responding with increasing FR requirements. Conversely, the HAD2 and LE had shorter SSRTs and lower levels of operant alcohol self-administration. However, for 2-bottle choice drinking HAD2s and P rats consumed more EtOH and had a greater preference for EtOH compared to LE.
Conclusions: These data extend previous findings showing the P rats to have increased delay discounting (decision-making impulsivity) and suggest that P rats also have a lack of behavioral inhibition (motor impulsivity). This supports the notion that P rats are a highly impulsive as well as "high-seeking" model of alcoholism, and that the HAD2s' elevated levels of alcohol consumption are not mediated via appetitive processes or impulsivity.
Haines K, Smith N, Czachowski C Alcohol Clin Exp Res (Hoboken). 2024; 49(2):476-487.
PMID: 39725675 PMC: 11828967. DOI: 10.1111/acer.15518.
Balan I, Grusca A, Chery S, Materia B, OBuckley T, Morrow A Life (Basel). 2024; 14(7).
PMID: 39063614 PMC: 11277648. DOI: 10.3390/life14070860.
Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats.
Katner S, Sentir A, Steagall K, Ding Z, Wetherill L, Hopf F Brain Sci. 2022; 12(8).
PMID: 36009105 PMC: 9406111. DOI: 10.3390/brainsci12081042.
Assessing Impulsivity in Humans and Rodents: Taking the Translational Road.
Esteves M, Moreira P, Sousa N, Leite-Almeida H Front Behav Neurosci. 2021; 15:647922.
PMID: 34025369 PMC: 8134540. DOI: 10.3389/fnbeh.2021.647922.
Neural correlates of inhibitory control are associated with stimulant-like effects of alcohol.
Weafer J, Gorka S, Dzemidzic M, Kareken D, Phan K, de Wit H Neuropsychopharmacology. 2021; 46(8):1442-1450.
PMID: 33947965 PMC: 8208996. DOI: 10.1038/s41386-021-01014-5.