Differential effects of response-contingent and response-independent nicotine in rats.

Passive administration of nicotine activates the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system. However, little is known about the effects of self-administered nicotine. Drug-naive rats were trained to respond for food reinforcement and then tested in one, 1-h session in which they received response-contingent i.v. nicotine or response-independent i.v. nicotine or saline. Blood draws were taken immediately prior to the session, 15 min after the first infusion and immediately after the session. Both response-contingent and response-independent nicotine (RI/N) increased corticosterone within 15 min, however, corticosterone levels returned to baseline in animals receiving response-contingent nicotine (RC/N) by the end of the session while remaining elevated in those receiving RI/N. Furthermore, only RI/N increased plasma epinephrine and norepinephrine levels; RC/N produced no effect. These differences indicate that nicotine's acute effects are powerfully modified by the presence of a contingency relationship between drug administration and the animal's behavior and that this relationship develops very rapidly.

Acquisition of nicotine self-administration in rats: the effects of dose, feeding schedule, and drug contingency.

The studies presented here were designed to further clarify the nature of nicotine self-administration (SA) based on a limited access model in which rats are food restricted, receive operant training using food reinforcement, and are then tested in daily 1-h drug sessions. We examined the effects of dose, feeding schedule, and contingency of drug delivery on acquisition of nicotine SA. Two doses of nicotine bitartrate, 0.03 and 0.06 mg/kg per infusion (free base), supported the transition from food-reinforced to drug-reinforced responding, although the pattern of behavior differed between these doses. In contrast, 0.01 mg/kg per infusion failed to maintain nicotine SA. In a second study, animals were divided into three groups according to feeding schedule. Rats that were both weight restricted and food deprived showed the highest level of SA behavior, although neither food deprivation nor weight restriction was necessary to establish SA. In the third experiment, rats that were switched from food to nicotine as the response-dependent reinforcer maintained higher response rates throughout a 9-day period than animals switched to response-independent (i.e., yoked) nicotine which showed minimal responding after day 1. Furthermore, the differences between self-administering and yoked animals emerged during the first session, suggesting that nicotine may serve as a reinforcer during the first drug exposure in naive animals. These results indicate that acquisition of nicotine SA can be influenced by both dose of nicotine and feeding schedule and that, in animals previously trained on a food-reinforced operant, active lever pressing is maintained only when nicotine delivery is contingent upon responding.

Tin distribution in adult and neonatal rat brain following exposure to triethyltin.

The uptake, distribution, and elimination of tin were determined in adult and neonatal (Postnatal Day 5) rat brain following ip administration of triethyltin bromide (TET). Groups of five adult CD rats were killed at 10 min, 1 hr, 4 hr, 24 hr, 5 days, or 10 days following acute exposure to 6.0 mg/kg TET; an additional group of adult animals was killed at 24 hr following exposure to either 3.0, 6.0, or 9.0 mg/kg (N = 5/dosage). The time course for tin distribution in 5-day-old rat pups was determined by killing pups 10 min, 30 min, 1 hr, 4 hr, 8 hr, 12 hr, 24 hr, 5 days, 10 days, or 22 days following exposure to either 3.0 or 6.0 mg/kg TET (N = 4/dosage/time). Tin analyses were performed by flameless atomic absorption spectrophotometry. The t1/2 for total tin in the adult rat brain following 6.0 mg/kg TET was determined to be 8.0 days. The maximum concentration in the adult was reached at 24 hr and corresponded to 4.6, 9.6, and 16.6 ng tin/mg protein for dosages of 3.0, 6.0, and 9.0 mg/kg, respectively. Tin was evenly distributed across all brain areas studied. For animals exposed to 6.0 mg/kg TET on Postnatal Day 5, the t1/2 for total tin in the brain was 7.3 days. A maximum concentration of 9.9 ng tin/mg protein was reached at 8 hr postexposure. The rate of elimination of tin from the brain (as measured by the elimination rate constant kel) did not differ significantly between adults and neonates. However, due to a dilution effect by the rapid brain growth of the neonate, the concentration of tin in the neonatal brain following TET administration decreased significantly faster than that in the adult.