Nine Generations of Selection for High and Low Nicotine Intake in Outbred Sprague–Dawley Rats

Abstract

Previous animal studies have revealed significant involvement of genetics in nicotine intake; however, the extent of the genetic contribution to this behavior has not been well addressed. We report the first study of nine generations of selection for high and low voluntary nicotine intake in outbred Sprague–Dawley rats. Bidirectional mass selection resulted in progressively greater nicotine consumption in the high nicotine-preferring line but no decrease in nicotine intake in the low nicotine-preferring line across generations. Our estimated realized heritability for high voluntary nicotine intake is 0.26 vs close to zero for low voluntary nicotine intake. In contrast, we found no differences between the lines across generations for saccharine intake. These selected lines may provide useful animal models for identifying susceptibility and resistance genes and variants for controlling voluntary nicotine intake in rodents, although we recognize that more generations of selection of these two lines and independent replication of our selection for high and low nicotine-preferring lines are needed.

Novelty Seeking and Drug Addiction in Humans and Animals: From Behavior to Molecules

“…Li and colleagues determined that the heritability of smoking initiation among humans ranges from 0.37 to 0.55 and that of smoking persistence is 0.46 to 0.59 (Li et al, 2003). Nesil and colleagues demonstrated that the heritability for high nicotine intake was 0.26 in rats after nine generations of selective breeding (Nesil et al, 2013). Heritability for amphetamine self-administration was estimated to be 0.74 among inbred rats (Meyer et al, 2010) and that for cocaine abuse in humans ranges from 0.42 to 0.79 (Agrawal et al, 2012).…”

Nicotine withdrawal in selectively bred high and low nicotine preferring rat lines

“…We reported the first nicotine preference lines from outbred Sprague Dawley rats by using bidirectional mass selection for voluntary oral nicotine intake behavior. Our results indicate that selective breeding of rats for high voluntary nicotine intake behavior resulted in increased nicotine consumption with a realized heritability of 0.26 after nine generations of selection (Nesil et al, 2013). Selection of a nicotine preference trait over the generations can increase vulnerability to the reinforcing effects of nicotine, but it can also increase sensitivity to the negative effects of nicotine withdrawal, which contributes to nicotine addiction and the maintenance of nicotine intake.…”

“…We have recently reported the first study of nine generations of selection for high and low voluntary nicotine intake behavior in outbred Sprague Dawley rats using an oral self-administration paradigm (Nesil et al, 2013). In the current study we used the rats from the F 8 generation and evaluated the effect of selection for high and low nicotine preference on response to nicotine withdrawal and resumption of intake.…”

Commonalities and Distinctions Among Mechanisms of Addiction to Alcohol and Other Drugs

“…Recently, lines of rats have been directionally selected for high vs low nicotine intake, but these animals have not yet been studied for other traits to date (Nesil et al, 2013). Tamara Phillips’ laboratory has been pursuing genetic contributions to methamphetamine self-administration in mice derived from C57BL/6J × DBA/2J crosses through repeated selections for high versus low voluntary drinking.…”