R.M. Booze

Intra-accumbal Tat1–72 alters acute and sensitized responses to cocaine

The effects of Tat, an HIV-1 protein, on intravenous cocaine-induced locomotor activity were examined in ovariectomized rats. Animals were habituated to activity chambers, administered an i.v. baseline/saline injection, and 24 h later, received bilateral, intra-accumbal microinjections of Tat1-72 (15 microg/microl) or vehicle. Twenty four hours later, rats received the first of 14 daily i.v. cocaine injections (3.0 mg/kg/inj, 1 /day) or saline. Locomotor activity was measured in automated chambers for 30 min following baseline and after the 1st and 14th cocaine injections. Observational time sampling following cocaine was also performed. Following acute cocaine/saline, Tat significantly increased cocaine-induced total activity over the 30-min session, with no significant effects for activity in the central compartment. Repeated cocaine injections produced behavioral sensitization with approximately 2-fold higher levels of total activity, approximately 3-fold higher levels of centrally directed activity, and increased locomotor scores via direct observations. Following repeated cocaine/saline, Tat altered the development of cocaine-induced behavioral sensitization for total activity with prior Tat exposure attenuating the development of cocaine-induced sensitization. Collectively, these data show that bilateral microinjection of Tat into the N Acc alters i.v. cocaine-induced behavior, suggesting that Tat produces behavioral changes by disrupting the mesocorticolimbic pathway.

Testing environment shape differentially modulates baseline and nicotine-induced changes in behavior: Sex differences, hypoactivity, and behavioral sensitization

ABSTRACT In those who use nicotine, the likelihood of dependence, negative health consequences, and failed treatment outcomes differ as a function of gender. Women may be more sensitive to learning processes driven by repeated nicotine exposure that influence conditioned approach and craving. Sex differences in nicotines influence over overt behaviors (i.e. hypoactivity or behavioral sensitization) can be examined using passive drug administration models in male and female rats. Following repeated intravenous (IV) nicotine injections, behavioral sensitization is enhanced in female rats compared to males. Nonetheless, characteristics of the testing environment also mediate rodent behavior following drug administration. The current experiment used a within‐subjects design to determine if nicotine‐induced changes in horizontal activity, center entries, and rearing displayed by male and female rats is detected when behavior was recorded in round vs. square chambers. Behaviors were recorded from each group (males‐round: n = 19; males‐square: n = 18; females‐square: n = 19; and females‐round: n = 19) immediately following IV injection of saline, acute nicotine, and repeated nicotine (0.05 mg/kg/injection). Prior to nicotine treatment, sex differences were apparent only in round chambers. Following nicotine administration, the order of magnitude for the chamber that provided enhanced detection of hypoactivity or sensitization was contingent upon both the dependent measure under examination and the animals biological sex. As such, round and square testing chambers provide different, and sometimes contradictory, accounts of how male and female rats respond to nicotine treatment. It is possible that a central mechanism such as stress or cue sensitivity is impacted by both drug exposure and environment to drive the sex differences observed in the current experiment. Until these complex relations are better understood, experiments considering sex differences in drug responses should balance characteristics of the testing environment to provide a complete interpretation of drug‐induced changes to behavior. HIGHLIGHTSMale and female rats display different levels activity prior to drug administration when tested in round, but not square chambers.The testing environment modulates nicotine‐induced depression of activity and behavioral sensitization.Interpretation of nicotine‐induced behavioral sex differences require that both round and square testing chambers are included in experiments.