Effects Of Pre-test Administration Research Articles

Activation of the Nitric-Oxide System in Nucleus Accumbens Inhibits the Nicotine Reversal Effects upon Ethanol-Induced Amnesia

The present study investigated the possible involvement of the nucleus accumbens’ (NAc) nitric oxide system in nicotine's reversal effect upon ethanol-induced amnesia. The hypothesis was tested through ethanol state-dependent memory assessment in adult male Wistar rats. Bilateral chronic cannulae were implanted in the NAc and the animals were trained in a step-through type inhibitory avoidance memory task. The step-through latency was examined 24 h after animals’ training. The pre-training or pre-test intraperitoneal (i.p.) injection of ethanol (0.9 g/kg) decreased the step-through latency, indicating an amnesic effect of the drug. Meanwhile, the pre-test administration of ethanol (0.6 and 0.9 g/kg) could reverse the pre-training ethanol (0.9 g/kg)-induced amnesia, suggesting a state-dependent effect. Similar to ethanol, the pre-test intra-NAc microinjection of nicotine (0.25 and 0.5 µg/rat) alone or nicotine (0.1, 0.25 and 0.5 µg/mouse, intra-NAc) in combination with an ineffective dose of ethanol (0.3 g/kg) could significantly reverse the (pre-training) ethanol-induced memory impairment. The ethanol (0.9 g/kg)-induced amnesia was similarly prevented following the pre-test intra-NAc administration of a nitric oxide synthase (NOS) inhibitor, L-NAME (0.4 and 0.8 µg/rat). Of note, the co-administration of L-NAME (0.04 and 0.08 µg/rat, intra-NAc) with an ineffective dose of nicotine (0.1 µg/rat, intra- NAc) could significantly potentiate the memory-improving effect of nicotine on ethanol-induced amnesia and resembled the effects of pre-test administration of a higher dose of nicotine. Furthermore, while the pre-test intra-NAc injection of L-NAME impaired the memory retrieval by itself, the pre-test intra-NAc administration of L-arginine, a nitric oxide precursor (0.3 and 0.6 µg/rat, intra-NAc), did not exert any effect either alone or in combination with an effective dose of nicotine (0.5 µg/rat, intra-NAc) on pre-training ethanol-induced memory impairment. Our findings indicated a possible role of the nucleus accumbens’ nitric oxide system in the improving effects of nicotine on ethanol-induced amnesia and the related state-dependent learning.

A dose–response study of the effects of pre-test administration of beta-adrenergic receptor antagonist propranolol on the learning of active place avoidance, a spatial cognition task, in rats

The involvement of various neurotransmitter receptors in the brain in the regulation of spatial behavior is a focus of interest for many cognitive neuroscientists. Active allothetic place avoidance (AAPA) task have been demonstrated to require spatial mapping and cognitive coordination and is highly dependent upon hippocampus. The present study was designed to evaluate the role of beta-adrenergic receptors in the modulation of locomotor and spatial behavior in this task. Four doses of centrally active beta-adrenergic antagonist propranolol (5, 20, 25 and 30 mg/kg) were administered intraperitoneally 30 min prior to testing in the place avoidance task. Four daily sessions were pursued, each lasting 20 min. A dose of 25 mg/kg was found to induce a deficit in spatial behavior (measured by number of entrances into the shock sector) without altering locomotion; lower doses were without effect. The highest dose (30 mg/kg) impaired both locomotion and avoidance behavior. The results suggest that beta-adrenoceptors are involved in the regulation of behavior in the place avoidance task and that it is possible to dissociate the effect of propranolol on the spatial performance and locomotion in the AAPA using dose-selection.

Effects of ultra-low doses of morphine, naloxone and ethanol on morphine state-dependent memory of passive avoidance in mice

This experiment examined and compared the effects of pre-test administration of morphine, naloxone and ethanol, at doses in the range of milligram/kg to those of nanogram/kg, on morphine state-dependent learning in a step-down passive avoidance task in mice. Morphine (5 mg/kg) administered before training impaired retention tested 24 hours later, but when the same dose of morphine was also administered before the test, the retention was significantly restored. Pre-training administration of 10 or 20 ng/kg (i.p.) of morphine had no effect, but when co-administered with the same drug at 5 mg/kg (s.c.), it prevented significantly the memory recall improvement after the administration of morphine (5 mg/kg, s.c.) alone. In a parallel experiment, naloxone (5 mg/kg) prevented the memory recall improvement by morphine. However, the effects of naloxone at doses in the range of ng/kg were opposite to those of milligram doses of the same drug. Pre-test administration of ethanol (1 mg/kg) improved memory recall and mimicked the effects of pre-test morphine administration. At doses in the nanogram range, the effects of ethanol were opposite those of mg/kg of the drug. A review of the literature indicates that, for several drugs and chemicals, the effects of nanogram doses are the opposite of the effects of milligrams, because different doses have different sites as well as mechanisms of actions. In conclusion, from the above results one may suggest that, in determination of the dose-response of at least some drugs, the study of the effects of doses much lower than two orders of magnitude of the minimum effective dose are warranted.