Mouse-killing in the rat: effects of sensory deficits on attack behaviour and stereotyped biting.

Sensory transections were performed in rats that killed mice after food-deprivation and subsequent satiation. Following partial maxillary or combined maxillary and optic deafferentation, but not after optic lesions alone, the number of mouse-kills declined sharply. This decline was accounted for by approximately a 50 per cent decrease in the number of mouse-presentations in which attack-behaviour took place and in the occurrence of attack-behaviour that did not always lead to a kill because rats frequently failed to bite. Furthermore, examination of killed mice revealed a shift in the distribution of body-bites away from the rostral regions normally seized by rats to more caudal areas of the mouse's body. Results indicate that certain stimulus-characteristics of mice mediated by the maxillary and optic nerves are important determinants of attack-behaviour and stereotyped biting in the rat.     

The influence of target sex and dominance on evoked attack in Rhesus monkeys

Attack behaviors were elicited by the electrical stimulation of the hypothalamus of freely moving male rhesus monkeys. The influence of the sex and dominance status of target animals on the evoked response was measured. Animals offered as targets were dominant males and females and subordinate males and and females. Males were attacked more often than females and subordinate targets of either sex were attacked more often than dominant targets. A comparison was made between spontaneous and evoked attack behavior.     

Studies on tube restraint-induced attack on a metal target by laboratory mice

This study examines factors influencing the attack on a metal target by laboratory ‘TO’ strain mice confined within a narrow perspex tube and contrasts this form of behaviour with attack seen in less equivocal forms of ‘aggression test’. The effects of sex, housing condition, reproductive experience, density, anosmia and castration (in the male) were systematically examined. This ‘model’ of ‘aggression’ shows few parallels with social conflict, parental defense and electroshock-induced forms of attack as none of the above manipulations influenced the level of target biting in this situation. Thus, in spite of claims that tube restraint-induced attack may show parallels with intermale aggression, the data suggest that it involves a totally different motivation.     

Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes

Many smokers attempt to quit smoking but few are successful in the long term. The heritability of nicotine addiction and smoking relapse have been documented, and research is focused on identifying specific genetic influences on the ability to quit smoking and response to specific medications. Research in genetically modified cell lines and mice has identified nicotine acetylcholine receptor subtypes that mediate the pharmacological and behavioral effects of nicotine sensitivity and withdrawal. Human genetic association studies have identified single nucleotide polymorphisms (SNPs) in genes encoding nicotine acetylcholine receptor subunits and nicotine metabolizing enzymes that influence smoking cessation phenotypes. There is initial promising evidence for a role in smoking cessation for SNPs in the β2 and α5/α3/β4 nAChR subunit genes; however, effects are small and not consistently replicated. There are reproducible and clinically significant associations of genotypic and phenotypic measures of CYP2A6 enzyme activity and nicotine metabolic rate with smoking cessation as well as response to nicotine replacement therapies and bupropion. Prospective clinical trials to identify associations of genetic variants and gene–gene interactions on smoking cessation are needed to generate the evidence base for both medication development and targeted therapy approaches based on genotype.     

Effects of a selective cannabinoid CB2 agonist and antagonist on intravenous nicotine self administration and reinstatement of nicotine seeking

Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2) have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio) and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg) and CB2 agonist AM1241 (1 to 10 mg/kg) on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 μg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior.     

Effects of nicotine on bone and calciotropic hormones in aged ovariectomized rats

The objective of this investigation was to assess the effects of chronic nicotine administration on bone status and serum calcium and calciotropic hormone levels in aged, estrogen-replete (intact, sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight-month-old sham-operated (sham) and ovariectomized (ovx) retired breeder rats were maintained untreated for 3 months to allow for the development of osteopenia in the ovx group. The animals were then administered either saline, low dose nicotine (6.0 mg/kg/day), or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 3 months. Blood was drawn at necropsy for determination of serum nicotine, cotinine, Ca, PTH, 25(OH)D, and 1,25(OH)(2)D. Right tibiae were collected and processed undecalcified for cancellous and cortical bone histomorphometry. Histomorphometric endpoints evaluated at the proximal tibial metaphysis included cancellous bone volume (BV/TV), osteoclast surface (Oc.S), osteoid surface (OS), mineralizing surface (MS), mineral apposition rate (MAR), and bone formation rate (BFR). Histomorphometric endpoints evaluated at the tibial diaphysis included cortical area (Ct.Ar), marrow area (Ma.Ar), and periosteal and endocortical MS, MAR, and BFR. Ovariectomy resulted in lower cancellous BV/TV and Ct.Ar and higher cancellous, endocortical, and periosteal MS and BFR. The presence of nicotine in serum confirmed successful delivery of the drug via osmotic minipumps. Administration of nicotine at the high dose resulted in lower serum 25(OH)D levels but differences in serum Ca or PTH were not detected with either nicotine treatment. Differences with nicotine treatment were also not detected for Oc.S at the proximal tibia. While treatment with nicotine at the high dose resulted in higher MS and BFR, in both sham and ovx rats, there were no differences due to nicotine treatment in cancellous BV/TV. Marrow area was greater in rats treated with nicotine than in rats treated with vehicle. However, differences with nicotine treatment were not detected in Ct.Ar in either intact or ovx rats. Overall, these findings indicate that steady state nicotine exposure does not alter bone mass in intact or ovx rats but may have detrimental effects on body storage of vitamin D.     

Effects of prenatal administration of nicotine on amino acid pools,protein metabolism,and nicotine binding in the brain

The effects of nicotine on brain protein metabolism and on the properties of the nicotine binding site were investigated in newborn animals exposed to nicotine during gestation. Brain protein synthesis rates measured in vivo were lower by 18% in newborn of treated animals. Protein degradation rates measured in vitro in the presence of nicotine were lower by 13%. The effect was specific forl-(-) nicotine, sinced-(+)nicotine, nicotinic acid, or nicotinamide had no effect on degradation rates. Newborn brain amino acid levels, mainly nonessential amino acids and amino acids of putative neurotrans nitter function, were changed some-what; an increase in the level of taurine (13%), threonine (21%), serine (35%) and glycine (35%), and a decrease in lysine (14%) was observed in the offspring of nicotine treated animals (0.5 mg/kg, s.c., 2×daily throughout gestation). These changes could not account for the decrease in protein metabolism. Nicotine binding was higher by 25% in the offspring of animals exposed to nicotine during gestation. No such increase was found after treatment of adult rats with nicotine, indicating that the properties of the nicotine binding site change with age.     

Granzyme B activity in target cells detects attack by cytotoxic lymphocytes

Lymphocyte-mediated cytotoxicity via granule exocytosis operates by the perforin-mediated transfer of granzymes from CTLs and NK cells into target cells where caspase activation and other death pathways are triggered. Granzyme B (GzB) is a major cytotoxic effector in this pathway, and its fate in target cells has been studied by several groups using immunodetection. In this study, we have used a newly developed cell-permeable fluorogenic GzB substrate to measure this protease activity in three different living targets following contact with cytotoxic effectors. Although no GzB activity is measurable in CTL or NK92 effector cells, this activity rapidly becomes detectable throughout the target cytoplasm after effector-target engagement. We have combined the GzB substrate with a second fluorogenic substrate selective for caspase 3 to allow both flow cytometry and fluorescence confocal microscopy studies of cytotoxicity. With both effectors, caspase 3 activity appears subsequent to that of GzB inside all three targets. Overexpression of Bcl-2 in target cells has minimal effects on lysis, NK- or CTL-delivered GzB activity, or activation of target caspase 3. Detection of target GzB activity followed by caspase 3 activation provides a unique readout of a potentially lethal injury delivered by cytotoxic lymphocytes.     

Effects of inhaled nicotine on instrumental learning of blood pressure responses

The present study investigated the effects of biofeedback of arterial blood pressure on cortical, peripheral, and psychological measures and the dependence of these effects on nicotine. Four groups of subjects, nonsmokers, and habitual smokers who smoked cigarettes during the experimental sessions containing 0.3, 0.8, or 1.5 mg nicotine, respectively, participated in a feedback paradigm in which continuous feedback of mean blood pressure was provided for intervals of 8 s each. While tonic blood pressure did not differ between the groups, the ability to modulate blood pressure (under feedback conditions) was restricted in smokers as compared to nonsmoking subjects; increasing nicotine dosage was accompanied by poorer performance. Independently of habitual smoking and nicotine doses, heart rate increased during feedback and under conditions of blood pressure increase. In smokers, activity in the alpha band was reduced in a dose-dependent manner. Slow cortical potentials (SCPs) during the feedback interval varied with self-induced blood pressure changes in nonsmokers (blood pressure increase was accompanied by reduced surface-negative potential shifts and vice versa), while SCP variations during feedback conditions were small in smokers, more so under the influence of 0.3 and 0.8-mg nicotine, less so under 1.5 mg. Verbal reports suggest that awareness of performance strategies may not be a necessary variable for performance on the blood pressure regulation task.This experiment was supported by Reemtsma Inc. Hamburg, which also provided the experimental cigarettes.     

Effects of nicotine on oviducal blood flow and embryo development in the rat

Nicotine (5.0 mg/kg) was injected (s.c.) twice daily on Day 1 or Days 1-4 or 1-5 of pregnancy. Cumulative doses of nicotine retarded embryo cell cleavage and substantially reduced embryo cell number (saline vs nicotine: 42.5 +/- 1.7 vs 22.1 +/- 1.9 nuclei/embryo, at 12:00 h on Day 5; P less than 0.05). However, treatment for even 1 day (Day 1) significantly reduced cell number (saline vs nicotine: 42.5 +/- 1.7 vs 30.5 +/- 0.9, at 12:00 h day on Day 5; P less than 0.01). Nicotine injection also resulted in a marked and prolonged reduction in oviduct blood flow (pretreatment vs 90 min after nicotine: 0.61 +/- 0.06 vs 0.37 +/- 0.10 ml/min . g-1; P less than 0.005). The results indicate that, in the rat, even a brief exposure to nicotine, the chief alkaloid of tobacco, reduces oviducal blood flow and the rate of embryo cell proliferation. The embryo is therefore susceptible to the effects of nicotine before implantation.     

Incisal orientation and biting efficiency

Broad-edged 'spatulate' upper and lower incisors are distinctive of catarrhines and platyrrhines who use them in various ways to peel fruits, remove bark, and strip leaves from branches. The incisors of modern humans not only control the bite size of foods during ingestion, but often grip items in a number of non-food related tasks. Such uses have long been implicated for Neandertals as well. Despite the evolutionary importance of incision and the fact that the incisors feature prominently in clinical dentistry (via orthodontic practices designed both to correct incisal misalignments and adjust their orientation), little is known about what affects their functional efficiency. Few mechanical analyses of incisal action have been published and none that seem to take note of the mechanisms of both fracture and friction at the tooth-food interface. Here, we modeled the incisal tip as a wedge, finding that the efficiency of biting foods that fracture elastically is strongly dependent on both the apex angle of the incisor and the coefficient of friction. Based on apex angle measurements from a small sample of human central incisors, the overall efficiency of upper central incisors is predicted to be greatest when the angle between the apex bisector and the direction of applied force is zero. However, this is complicated greatly by friction, particularly for the lower incisors. The analysis probably applies not only to the use of incisors by humans, but also to some extent to frugivorous primates. This model should clarify the mechanics behind incision and can provide a basic foundation upon which more advanced models can be built on in the future.     

Effects of 'local' clutter on human target detection

In theory, properties of clutter can be defined globally or locally. However, in the literature, the distinction between local and global clutter is arbitrary, where the standard approach of setting the local domain to twice the expected target size, in applying local clutter metrics, is adopted without any justification. This paper addresses this problem and considers the implications for the application of clutter metrics. It was found that the size of the local clutter region around a target has a strong effect on the probability of detection of that target and that this is affected by regions much larger than twice the target size. It was also discovered that this effect was much stronger for targets subtending less than 0.8 degrees of visual angle than for larger targets. In the case of the former, the fall-off in human visual performance with clutter region size was approximately quadratic, compared to a slight linear fall-off for larger targets. A simple model is presented explaining these phenomena, indicating that the auto-covariance function characterising the clutter is the main determinant of the size of the region of local clutter.     

Effects of nicotine on the fertility, cytology and life span of male rats

Contrary to an earlier opinion that nicotine has no effect on the fertility of male animals or humans, the present experimental study using male inbred Fisher rats demonstrates that the reproductive capacity of the animals is greatly reduced when injected with nicotine, and that the effect is much greater in male than in female Fisher rats similarly injected with nicotine. This is in accord with some earlier histological and morphological studies which have shown that female rodents have a greater tolerance to nicotine than their male counterparts. It is also confirmed by the cytologic observations of the present study. These observations show that, similar to female rats, inflammatory processes, as evidenced by an increased number of lymphocytes and/or polymorphonuclear leukocytes, are responsible for the decrease in fertility. However, the cytological profile is profoundly different in the two sexes: virulent inflammatory conditions begin much earlier in male rats, they are more frequent and, whereas the condition is reversible in the female animal when nicotine treatment is discontinued, it is not in some male rats, and inflammatory conditions persist for the entire life as does infertility. However, the life span of nicotine-treated male rats is greater than in female nicotine-treated rats, although it is shorter in both sexes than in their respective controls; in some male nicotine-treated rats, the life span is greater not only than in their male controls but even than in their female counterparts. Possible explanations for this apparently paradoxical life-prolonging effect of nicotine treatment are reviewed, but the evidence is either conflicting or insufficiently established and requires further study.