Differential Neuroendocrine and Behavioral Responses to Cocaine in Lewis and Fischer Rats

Abstract

Lewis (LEW) and Fischer 344 (F344) rats differ in responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis as well as in their behavioral responses to drugs of abuse. The present experiments were conducted to compare hypothalamic corticotropin-releasing factor (CRF), plasma adrenocorti-cotropic hormone (ACTH) and plasma corticosterone (CS) responses to cocaine (0–60 mg/kg, i.p.) in LEW and F344 rats. Acute administration of cocaine resulted in decreases in CRF and dose-related increases in CS and ACTH with significant differences observed between the strains. Cocaine also increased plasma norepinephrine concentrations. Although the CS response was increased in the F344 compared to LEW rats, the percent change in the CS response was markedly enhanced in LEW rats. Plasma ACTH concentrations as well as the percentage of the control response were dramatically increased at the 40 mg/kg cocaine dose in the LEW compared to F344 rats. Since cocaine-induced changes in HPA axis activity may contribute to behavioral responses to cocaine, another experiment was performed to compare the locomotor responses to novelty and to acute cocaine between LEW and F344 rats. Strain differences were not observed in the locomotor response to novelty or to cocaine. These data indicate that strain differences exist in the neuroendocrine response to acute cocaine exposure.

Strain differences in response to escapable and inescapable novel environments and their ability to predict amphetamine-induced locomotor activity

“…Consistent with the results of the present study that utilized a circular locomotor apparatus, other studies using a different inescapable environment, the open field, report that F344 rats show greater exploratory behavior as assessed by inner versus outer area movement ratio (Glowa et al 1992b;Sternberg et al 1992). In contrast to the results of the present study, some researchers report greater activity levels in Lewis rats in a novel, inescapable apparatus (Camp et al 1994;Ambrosio et al 1995;Rex et al 1996;Paulus et al 1998) but others report no strain differences (Kosten et al 1994b;Simar et al 1996;Stohr et al 1998). Differences in type of measure, procedure or apparatus may underlie these discrepancies across studies.…”

“…Compared to F344 rats, Lewis rats show greater conditioned place preference for drugs (Guitart et al 1992;Kosten et al 1994b;Horan et al 1997) and heightened acquisition of drug self-administration (Ambrosio et al 1995;Kosten et al 1997;Suzuki et al 1988). Yet, Lewis rats, compared to F344 rats, have blunted corticosterone levels both basally (Griffin and Whitacre 1991;Dhabhar et al 1993;Ortiz et al 1995) and in response to acute cocaine administration (Simar et al 1996) or acute stress (Sternberg et al 1992;Dhabhar et al 1993). In contrast to the fairly consistent findings of strain differences in these behavioral and hormonal measures, studies of locomotor activity levels in a novel environment report conflicting results (Camp et al 1994;Kosten et al 1994b;Ambrosio et al 1995;Rex et al 1996;Stohr et al 1998;Haile et al 2001b).…”

Inbred Lewis and Fischer 344 rat strains differ not only in novelty- and amphetamine-induced behaviors, but also in dopamine transporter activity in vivo

“…Earlier reports on response to novelty in these rat strains have been somewhat inconsistent (Camp et al 1994;Rex et al 1996;Simar et al 1996;Stöhr et al 1998;Haile et al 2001;Miserendino et al 2003). Methodological differences, as well as established strain differences to stress, likely contributed to these conflicting results.…”

The amphetamine sensitization model of schizophrenia: relevance beyond psychotic symptoms?

“…As an example, stress-or drug-induced corticosterone release is attenuated in Lewis compared to Fischer rats (Simar et al 1996). Cador et al suggested that rats with a high stress-induced corticosterone release show higher amphetamine-induced locomotion and are more likely to develop amphetamine self-administration (Cador et al 1993).…”