Sex differences in tolerance to the locomotor depressant effects of lobeline in periadolescent rats

Abstract

Lobeline is being tested in clinical trials as a pharmacotherapy for methamphetamine abuse and attention deficit hyperactivity disorder. Preclinical research demonstrates that lobeline produces locomotor hypoactivity apart from its therapeutic effects; however, the hypothesis that there are sex differences in hypoactivity or in the development of tolerance to its locomotor depressant effects has not been investigated. Periadolescent rats were injected with saline to determine baseline locomotor activity. Animals received saline or lobeline (1.0-10 mg/kg) daily for 7 consecutive days (post natal days 29-35), and were challenged with saline 24 h later to assess baseline activity. Lobeline produced hypoactivity in total horizontal activity and center distance travelled. Tolerance developed to the lobeline-induced hypoactivity and sex differences in lobeline tolerance were observed on both measures. Females acquired tolerance to lobeline 5.6 mg/kg at a slower rate than males. Saline challenge revealed a linear dose-dependent trend of hyperactivity on both measures, which indicates that rats exhibited altered locomotor behavior 24 h after the final lobeline treatment. These findings demonstrate sex differences in the hypoactive response to lobeline prior to puberty and suggest that females may experience more locomotor depressant effects than males. Chronic lobeline may induce hyperactivity following cessation of treatment.

Lobeline attenuates neonatal ethanol-mediated changes in hyperactivity and dopamine transporter function in the prefrontal cortex in rats

“…The decrease in activity observed following lobeline (3 mg/kg) in control rats is consistent with previous reports (Damaj et al, 1997; Miller et al, 2003; Harrod and Van Horn, 2009). Tolerance developed to the hypoactivity upon repeated lobeline administration (Miller et al, 2003; Harrod and Van Horn, 2009). Therefore, while lobeline specifically attenuates neonatal ethanol-induced hyperactivity, specificity occurred only across a narrow dose range.…”

Intravenous Prenatal Nicotine Exposure Alters METH-Induced Hyperactivity, Conditioned Hyperactivity, and BDNF in Adult Rat Offspring

“…The defining characteristic of Pavlovian learning is that the conditional stimulus (CS) elicits a conditional response from the animal when the stimulus is presented alone, in the absence of the unconditional stimulus (US) [68]. The form of the CR may be the same or the opposite of the unconditional response (UR) produced by the drug [38,47,69]. In the present experiment, exposure to the locomotor activity chambers (i.e., the CS) elicited increased activity and center distance travelled (CR) in the absence of METH (i.e., the US).…”

Genetically expressed HIV-1 viral proteins attenuate nicotine-induced behavioral sensitization and alter mesocorticolimbic ERK and CREB signaling in rats

“…This was done so that the onset of nicotine’s effects did not overlap with the period that rats showed the most exploratory behavior in the chamber, which was during the first 15 min. Previous research indicates that control rats exhibit asymptotic levels of within-session habituation by 20 to 30 min, according to similar procedures and use of the same automated chambers (Harrod et al, 2008; Harrod and Van Horn, 2009). Rats were administered nicotine or saline subcutaneously every day for a total of 20 days.…”