Selective breeding for high alcohol consumption and response to nicotine: locomotor activity, dopaminergic in the mesolimbic system, and innate genetic differences in male and female alcohol-preferring, non-preferring, and replicate lines of high-alcohol drinking and low-alcohol drinking rats

Gerald A. Deehan, Sheketha R. Hauser, Bruk Getachew, R. Aaron Waeiss, Eric Engleman, Christopher P. Knight, William J. McBride, William Truitt, Richard Bell, Zachary Rodd

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Rationale: There is evidence for a common genetic link between alcohol and nicotine dependence. Rodents selectively bred for high alcohol consumption/responsivity are also more likely to self-administer nicotine than controls. Objectives: The experiments examined the response to systemic nicotine, the effects of nicotine within the drug reward pathway, and innate expression of nicotine-related genes in a brain region regulating drug reward/self-administration in multiple lines of rats selectively bred for high and low alcohol consumption. Methods: The experiments examined the effects of systemic administration of nicotine on locomotor activity, the effects of nicotine administered directly into the (posterior ventral tegmental area; pVTA) on dopamine (DA) release in the nucleus accumbens shell (AcbSh), and innate mRNA levels of acetylcholine receptor genes in the pVTA were determined in 6 selectively bred high/low alcohol consuming and Wistar rat lines. Results: The high alcohol-consuming rat lines had greater nicotine-induced locomotor activity compared to low alcohol-consuming rat lines. Microinjections of nicotine into the pVTA resulted in DA release in the AcbSh with the dose response curves for high alcohol-consuming rats shifted leftward and upward. Genetic analysis of the pVTA indicated P rats expressed higher levels of α2 and β4. Conclusion: Selective breeding for high alcohol preference resulted in a genetically divergent behavioral and neurobiological sensitivity to nicotine. The observed behavioral and neurochemical differences between the rat lines would predict an increased likelihood of nicotine reinforcement. The data support the hypothesis of a common genetic basis for drug addiction and identifies potential receptor targets.

Original languageEnglish (US)
JournalPsychopharmacology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Locomotion
Nicotine
Alcohol Drinking
Alcohols
Reward
Dopamine
Selective Breeding
Tobacco Use Disorder
Ventral Tegmental Area
Self Administration
Nucleus Accumbens
Microinjections
Cholinergic Receptors
Pharmaceutical Preparations
Alcoholism
Genes
Substance-Related Disorders
Wistar Rats
Rodentia
Messenger RNA

Keywords

  • Alcohol-preferring P rats
  • Dopamine
  • High-alcohol-drinking HAD rats
  • Locomotor activity
  • Nicotine
  • Nucleus accumbens
  • Ventral tegmental area

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{99e4dbe41f824c27b56e25f4cf10bc94,
title = "Selective breeding for high alcohol consumption and response to nicotine: locomotor activity, dopaminergic in the mesolimbic system, and innate genetic differences in male and female alcohol-preferring, non-preferring, and replicate lines of high-alcohol drinking and low-alcohol drinking rats",
abstract = "Rationale: There is evidence for a common genetic link between alcohol and nicotine dependence. Rodents selectively bred for high alcohol consumption/responsivity are also more likely to self-administer nicotine than controls. Objectives: The experiments examined the response to systemic nicotine, the effects of nicotine within the drug reward pathway, and innate expression of nicotine-related genes in a brain region regulating drug reward/self-administration in multiple lines of rats selectively bred for high and low alcohol consumption. Methods: The experiments examined the effects of systemic administration of nicotine on locomotor activity, the effects of nicotine administered directly into the (posterior ventral tegmental area; pVTA) on dopamine (DA) release in the nucleus accumbens shell (AcbSh), and innate mRNA levels of acetylcholine receptor genes in the pVTA were determined in 6 selectively bred high/low alcohol consuming and Wistar rat lines. Results: The high alcohol-consuming rat lines had greater nicotine-induced locomotor activity compared to low alcohol-consuming rat lines. Microinjections of nicotine into the pVTA resulted in DA release in the AcbSh with the dose response curves for high alcohol-consuming rats shifted leftward and upward. Genetic analysis of the pVTA indicated P rats expressed higher levels of α2 and β4. Conclusion: Selective breeding for high alcohol preference resulted in a genetically divergent behavioral and neurobiological sensitivity to nicotine. The observed behavioral and neurochemical differences between the rat lines would predict an increased likelihood of nicotine reinforcement. The data support the hypothesis of a common genetic basis for drug addiction and identifies potential receptor targets.",
keywords = "Alcohol-preferring P rats, Dopamine, High-alcohol-drinking HAD rats, Locomotor activity, Nicotine, Nucleus accumbens, Ventral tegmental area",
author = "Deehan, {Gerald A.} and Hauser, {Sheketha R.} and Bruk Getachew and {Aaron Waeiss}, R. and Eric Engleman and Knight, {Christopher P.} and McBride, {William J.} and William Truitt and Richard Bell and Zachary Rodd",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00213-018-4970-0",
language = "English (US)",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Selective breeding for high alcohol consumption and response to nicotine

T2 - locomotor activity, dopaminergic in the mesolimbic system, and innate genetic differences in male and female alcohol-preferring, non-preferring, and replicate lines of high-alcohol drinking and low-alcohol drinking rats

AU - Deehan, Gerald A.

AU - Hauser, Sheketha R.

AU - Getachew, Bruk

AU - Aaron Waeiss, R.

AU - Engleman, Eric

AU - Knight, Christopher P.

AU - McBride, William J.

AU - Truitt, William

AU - Bell, Richard

AU - Rodd, Zachary

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Rationale: There is evidence for a common genetic link between alcohol and nicotine dependence. Rodents selectively bred for high alcohol consumption/responsivity are also more likely to self-administer nicotine than controls. Objectives: The experiments examined the response to systemic nicotine, the effects of nicotine within the drug reward pathway, and innate expression of nicotine-related genes in a brain region regulating drug reward/self-administration in multiple lines of rats selectively bred for high and low alcohol consumption. Methods: The experiments examined the effects of systemic administration of nicotine on locomotor activity, the effects of nicotine administered directly into the (posterior ventral tegmental area; pVTA) on dopamine (DA) release in the nucleus accumbens shell (AcbSh), and innate mRNA levels of acetylcholine receptor genes in the pVTA were determined in 6 selectively bred high/low alcohol consuming and Wistar rat lines. Results: The high alcohol-consuming rat lines had greater nicotine-induced locomotor activity compared to low alcohol-consuming rat lines. Microinjections of nicotine into the pVTA resulted in DA release in the AcbSh with the dose response curves for high alcohol-consuming rats shifted leftward and upward. Genetic analysis of the pVTA indicated P rats expressed higher levels of α2 and β4. Conclusion: Selective breeding for high alcohol preference resulted in a genetically divergent behavioral and neurobiological sensitivity to nicotine. The observed behavioral and neurochemical differences between the rat lines would predict an increased likelihood of nicotine reinforcement. The data support the hypothesis of a common genetic basis for drug addiction and identifies potential receptor targets.

AB - Rationale: There is evidence for a common genetic link between alcohol and nicotine dependence. Rodents selectively bred for high alcohol consumption/responsivity are also more likely to self-administer nicotine than controls. Objectives: The experiments examined the response to systemic nicotine, the effects of nicotine within the drug reward pathway, and innate expression of nicotine-related genes in a brain region regulating drug reward/self-administration in multiple lines of rats selectively bred for high and low alcohol consumption. Methods: The experiments examined the effects of systemic administration of nicotine on locomotor activity, the effects of nicotine administered directly into the (posterior ventral tegmental area; pVTA) on dopamine (DA) release in the nucleus accumbens shell (AcbSh), and innate mRNA levels of acetylcholine receptor genes in the pVTA were determined in 6 selectively bred high/low alcohol consuming and Wistar rat lines. Results: The high alcohol-consuming rat lines had greater nicotine-induced locomotor activity compared to low alcohol-consuming rat lines. Microinjections of nicotine into the pVTA resulted in DA release in the AcbSh with the dose response curves for high alcohol-consuming rats shifted leftward and upward. Genetic analysis of the pVTA indicated P rats expressed higher levels of α2 and β4. Conclusion: Selective breeding for high alcohol preference resulted in a genetically divergent behavioral and neurobiological sensitivity to nicotine. The observed behavioral and neurochemical differences between the rat lines would predict an increased likelihood of nicotine reinforcement. The data support the hypothesis of a common genetic basis for drug addiction and identifies potential receptor targets.

KW - Alcohol-preferring P rats

KW - Dopamine

KW - High-alcohol-drinking HAD rats

KW - Locomotor activity

KW - Nicotine

KW - Nucleus accumbens

KW - Ventral tegmental area

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U2 - 10.1007/s00213-018-4970-0

DO - 10.1007/s00213-018-4970-0

M3 - Article

AN - SCOPUS:85050612283

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

ER -