Effects of ventral striatal 6-OHDA lesions or amphetamine sensitization on ethanol consumption in the rat

Female rats with continuous access to water and 6% ethanol were given bilateral ventral striatal 6-OHDA infusions, which induced pronounced striatal depletions of dopamine. The postoperative ethanol consumption of these rats was not significantly affected in comparison to vehicle-infused controls. In a second experiment, female rats received escalating doses of d-amphetamine over a 5-week period (from 1 to 9 mg/kg/injection). Control females were given saline injections. Following a 3-month drug-free interval, the females were given access to ethanol, the concentration of which was gradually increased from 2% to 12% with weekly intervals. Amphetamine-sensitized rats consumed significantly more alcohol than the saline-treated controls. Taken together, these results suggest that striatal dopaminergic mechanisms, while not necessary for basal ethanol drinking, can facilitate alcohol drinking.     

Differential alterations in basal and D-amphetamine-induced behavioural pattern following 6-OHDA or ibotenic acid lesions into the dorsal striatum

It is well known that the corpus striatum is related to the sterotyped activation induced by several psychostimulants. In this study we analyzed the effects of 6-OHDA, in comparison with those of ibotenic acid lesions, into the dorsal striatum, on the behavioural pattern induced by saline or D-amphetamine treatment. A computerized technique for recording the animal motor activity was developed in order to define in a detailed way the behavioural profile in lesioned and sham-operated rats induced by the saline or D-amphetamine treatment. A 6-OHDA lesion into the dorsal striatum modified the basal behavioural pattern which was mainly characterized by reduced motor activation while ibotenic acid lesion affected the structure of the basal behavioral pattern. D-Amphetamine administration in 6-OHDA lesioned rats induced a behavioural stimulation, but a decreased motor and stereotyped activation was observed compared to the sham-operated animals treated with D-amphetamine. In contrast, D-amphetamine administration in the ibotenic acid-lesioned rats induced a motor and stereotyped activity which was not reduced compared to that seen after D-amphetamine treatment in sham-operated rats. These results suggest that these two types of lesion induced differential effects on the behavioural pattern either after saline or after D-amphetamine administration. Dopaminergic neurotransmission in the dorsal striatum plays a permissive role on the emergence of the behavioural responses, while the dorsal striatum circuitry plays a crucial role on the organization of the behavioural pattern. In addition, dopaminergic activity in this structure serves a primary control in the D-amphetamine-elicited motor activation or stereotypy, while the striatal structure is involved in the shaping of the D-amphetamine behavioural pattern.     

Lack of permanent nigrostriatal dopamine deficit following 6-hydroxydopamine injection into the rat striatum. Short communication

OBJECTIVE: Understanding the contributors to physical disability in older adults is an important component of the national health objective of expanding disability-free life by the year 2000. The purpose of this study was to determine the frequency with which older adults attribute their difficulty performing a number of common daily tasks to "old age" and to identify specific conditions and diseases associated with this attribution. Finally we sought to determine the characteristics that might differentiate persons able to attribute their disability to specific conditions from those who cite old age as the etiology of their disability. DESIGN: A cross-sectional, observational, study. SETTING: The Johns Hopkins Functional Status Laboratory. PARTICIPANTS: Two hundred thirty community-dwelling volunteers 60 years of age and older who could stand unassisted for > or = 1 minute and who were without cognitive impairment. MEASUREMENTS: A 1-day evaluation included physical performance evaluations, both performance-based and self-reported function for 27 tasks, and self-report of physician-diagnosed diseases. Those with difficulty in a task and those who denied difficulty but had changed the method of task performance (modification) because of an underlying health or physical condition were identified and asked to name the cause of their difficulty or task modification; options were specific diseases/medical conditions or "old age." The prevalence of "old age" citation as a cause of functional limitation, as well as its associated characteristics and medical conditions, was determined. MAIN RESULTS: Twenty percent of the 230 participants cited "old age" as the cause of their disability in two or more tasks. Tasks for which difficulty was most frequently attributed to "old age" were dressing oneself (31%), walking around the home (25%), walking 1/2 mile (5-6 blocks) (25%), cutting toenails (16%), getting in or out of a bed or chair or out a car (14% each), and ascending/descending stairs (13%). Significantly higher levels of arthritis, heart disease, and hearing loss were reported in persons attributing their disability to "old age" than in those not reporting "old age" as the cause of their disability. We found no differences in age, gender, race, education, or cognitive status for the two groups. However, individuals citing "old age" as the cause of functional decrements walked more slowly than those who cited a specific disease. CONCLUSIONS: These data suggest that a significant proportion of functional decline attributed to "aging" in older adults may be associated with specific conditions. Identifying and reducing the impact of these conditions may prove to be a useful approach to preventing or minimizing functional loss.     

Intracerebral injection of interferon-gamma inhibits the astrocyte proliferation following the brain injury in the 6-day-old rat

The present study examines the influence of interferon-gamma (IFN-gamma) on the astrocyte proliferation in the rat brain injured within the early period of postnatal development. Six-day-old male rats received a lesion in the left cerebral hemisphere and a single injection of recombinant rat IFN-gamma into the lesion cavity. One or 2 days after the injury the rats were injected with 3H-thymidine. Brain sections were immunostained for glial fibrillary acidic protein (GFAP), subjected to autoradiography, and examined microscopically to record proliferating GFAP-immunopositive astrocytes labeled with 3H-thymidine. In the IFN-gamma-injected rats, a statistically significant decrease in the intensity of reactive astrocyte proliferation was revealed. On day 1 after injury the intensity of astrocyte proliferation showed dose-dependent changes. Relations between the astrocyte reactivity and multiple factors existing in the injured and IFN-gamma-injected brain are discussed. The results represent the first in vivo evidence of a dose-dependent action of IFN-gamma on the astrocyte proliferation in response to injury.     

Cessation of drinking following intracranial injections of angiotensin in the rat.

Injection of angiotensin amide into the preoptic area is known to elicit drinking in rats that are in water balance. 2 experiments were conducted with a total of 15 male hooded rats. When Ss were injected with 10 ng. angiotensin and access to water was delayed for varying times, the dipsogenic effect of angiotensin lasted for 60-90 min. When access to water was not delayed, Ss stopped drinking after 8.5 min., indicating that the ingestion of water is satiating. When Ss were offered isotonic saline, they stopped drinking 11 min. after injection, indicating that satiation or inhibition of angiotensin-induced thirst can also occur when there are no osmotic changes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Compensatory changes in striatal dopamine neurons following recovery from injury induced by 6-OHDA or methamphetamine: A review of evidence from microdialysis studies.

Reviews microdialysis experiments by E. Casta?eda et al (1989, in press), T. E. Robinson and I. Q. Whishaw (1987, 1988), and Robinson et al (1990) involving the association between recovery from dopamine (DA) depletion and normalization of extracellular DA. Data suggest that the 3 behavioral outcomes (sparing, recovery, and loss of function) associated with DA depletion may be related to differences in the ability of the residual population of DA neurons to maintain extracellular concentrations of DA; this effect may vary with lesion size. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intergenerational transfer of individual differences in hereditary monarchs: Genetic, role-modeling, cohort, or sociocultural effects?

342 hereditary monarchs were drawn from 14 European nations. Ss, along with their parents, grandparents, and predecessors, were then assessed on the variables of intelligence, morality, eminence, leadership, life span, and reign span. Theoretically significant interaction effects were also operationalized, using such moderator variables as genetic relationship, years of overlap in lives, age difference, difference in reign midpoints, and sex. The intergenerational transfer of intelligence and life span was best explained by genetics, whereas the transfer of morality and eminence was governed by role-modeling processes. The remaining variables were either transferred by more complex mechanisms (leadership) or not transferred at all from one generation to the next (reign span). Results contradict both F. A. Woods's (1906) belief that morality is genetically inherited and F. Galton's (1869) argument that eminence can serve as a nearly equivalent proxy variable for intellectual genius. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D1 and D2 receptor regulation of preproenkephalin and preprodynorphin mRNA in rat striatum following acute injection of amphetamine or methamphetamine

From 1990 through 1993, we treated 36 patients with recurrent typical biliary colic but who showed no ultrasonic evidence of cholelithiasis by laparoscopic cholecystectomy. Associated symptoms included nausea (75%), bloating (56%), fatty-food intolerance (53%), vomiting (17%), weight loss (31%), bowel irregularity (28%), reflux or dyspepsia (25%), and fever (17%). Diagnostic evaluation included ultrasound (100%), upper gastrointestinal series (36%), oral cholecystogram (14%), computed tomographic scan (39%), endoscopic retrograde cholangiopancreatography (17%), upper gastrointestinal endoscopy (14%), and hepatobiliary scan (92%). Quantitative hepatobiliary scans in 33 patients revealed a low gallbladder ejection fraction (EF) of less than 35% in 29 patients (88%; mean EF = 9%), and 13 patients experienced reproducible pain after cholecystokinin provocation. All patients underwent attempted laparoscopic cholecystectomy; one case of unsuspected acute acalculous cholecystitis was converted to open laparotomy because of unclear anatomy. Gross and histological examination of the gallbladders revealed chronic inflammation (83%), cholesterolosis (31%), cholesterol crystals or small stones (17%), acute inflammation (8%), polyps (6%), and normal histology (6%); however, blind retrospective scoring of gallbladders revealed significant chronic inflammation in only 38%. In the 2 to 40 months (mean, 14 months) since operation, there have been no deaths (97% follow-up). Laparoscopic cholecystectomy relieved pain in 93% of patients with a low preoperative EF compared with 75% of patients with a normal EF (nonsignificant p value). Persistent abdominal or gastrointestinal complaints included flatulence (31%), loose stools or fecal urgency (29%), belching (29%), indigestion (20%), nausea (11%), and "typical" gallbladder pain (9%). We conclude that many patients with symptoms of biliary colic and scintigraphic evidence of biliary dyskinesia have histologic findings of chronic cholecystitis. Although laparoscopic cholecystectomy usually eliminates biliary colic, persistent nonbiliary complaints are frequent.     

An investigation into the effects of 5-HT agonists and receptor antagonists on ethanol self-administration in the rat

Pharmacological manipulation leading to altered 5-HT function has been widely demonstrated to reduce ethanol intake in free choice tests. The aim of the present study was to examine the effects of a range of compounds known to influence 5-HT neurotransmission, including selective 5-HT receptor agonists and antagonists, on ethanol ingestion and maintained behaviour in an operant self-administration paradigm. Female Sprague-Dawley rats were trained to respond for 8% ethanol (v/v) in a 60-min test by a previously described technique. The number of responses and ethanol reinforcers (dipper deliveries), ethanol consumption (g/kg of body weight), and locomotor activity (LMA) were measured following administration of 5-HT agonists (5-HT, d-fenfluramine, fluoxetine, buspirone, TFMPP, and DOI) and antagonists (metergoline, ritanserin, and ondansetron) 30 min prior to testing. d-Fenfluramine, fluoxetine, buspirone, TFMPP, and DOI all produced a reduction in ethanol ingestion and maintained behaviour at doses that failed to reduce LMA. Conversely, metergoline and ritanserin only reduced ethanol self-administration at doses that concomitantly reduced LMA. 5-HT and ondansetron were without effect on any measure. These results demonstrate that, under the present experimental conditions, activation of central 5-HT1A, 5-HT1B, and 5-HT2 receptors reduced ethanol intake and reinforced behaviour in an operant paradigm.     

Dexmedetomidine, diazepam, and propranolol in the treatment of ethanol withdrawal symptoms in the rat

In this study, the effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms, were compared with those of diazepam and propranolol. The rats were given highly intoxicating doses of ethanol for 4 days. After the intoxication period, rats were divided into four equal groups: a dexmedetomidine-treated group (30 micrograms/kg, sc), a diazepam-treated group (2 mg/kg, sc), a propranolol-treated group (5 mg/kg, sc), and a control group with no medication. Medication was given in the withdrawal phase-2, 8, 14, and 20 hr after the onset of the withdrawal symptoms. The severity of the ethanol withdrawal symptoms (rigidity, tremor, irritability, and hypoactivity) was observed up to 33 hr after the onset of the ethanol withdrawal symptoms. Both dexmedetomidine and diazepam significantly relieved tremor compared with the control group. Diazepam reduced irritability significantly, compared with the control group. When measured as the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability), dexmedetomidine and diazepam significantly relieved the ethanol withdrawal reaction. Propranolol attenuated tremor, but was inefficient against other withdrawal symptoms. Dexmedetomidine may thus represent a new effective drug in the treatment of the ethanol withdrawal syndrome.     

Understanding gender differences in bereavement following the death of an infant: Implications of or treatment.

The death of an infant confronts parents with a multitude of difficult challenges. Bereaved parents often experience a grief that is unexpectedly pervasive, intense and enduring. Support from family, friends, and medical professionals is often limited, and most parents rely predominantly on their partner or spouse for sustained support and understanding over time, partners often experience increased difficulties in supporting each other due to gender differences in grief and coping, strained communication, and characteristic patterns of misunderstandings. This article discusses research findings regarding gender similarities and differences in grief and coping following perinatal loss or loss from sudden infant death syndrome (SIDS), and regarding marital difficulties associated with incongruent grieving. Also discussed are the impact of social support on the experience of bereavement, typical patterns of misunderstandings underlying many grief-related marital difficulties, and treatment recommendations for psychotherapists working with individual clients or bereaved couples. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential regulation of GABA(A) receptor gene expression by ethanol in the rat hippocampus versus cerebral cortex

Previous research has shown that chronic ethanol consumption dramatically alters GABA(A) receptor alpha1 and alpha4 subunit gene expression in the cerebral cortex and GABA(A) receptor alpha1 and alpha6 subunit gene expression in the cerebellum. However, it is not yet known if chronic ethanol consumption produces similar alterations in GABA(A) receptor gene expression in other brain regions. One brain region of interest is the hippocampus because it has recently been shown that a subset of GABA(A) receptors in the hippocampus is responsive to pharmacologically relevant concentrations of ethanol. Therefore, we directly compared the effects of chronic ethanol consumption on GABA(A) receptor subunit gene expression in the hippocampus and cerebral cortex. Furthermore, we investigated whether the duration of ethanol consumption (14 or 40 days) would influence regulation of GABA(A) receptor gene expression in these two brain regions. Chronic ethanol consumption produced a significant increase in the level of GABA(A) receptor alpha4 subunit peptide in the hippocampus following 40 days but not 14 days. The relative expression of hippocampal GABA(A) receptor alpha1, alpha2, alpha3, beta(2/3), or gamma2 was not altered by either period of chronic ethanol exposure. In marked contrast, chronic ethanol consumption for 40 days significantly increased the relative expression of cerebral cortical GABA(A) receptor alpha4 subunits and significantly decreased the relative expression of cerebral cortical GABA(A) receptor alpha1 subunits. This finding is consistent with previous results following 14 days of chronic ethanol consumption. Hence, chronic ethanol consumption alters GABA(A) receptor gene expression in the hippocampus but in a different manner from that in either the cerebral cortex or the cerebellum. Furthermore, these alterations are dependent on the duration of ethanol exposure.     

Enhanced frustrative nonreward effect following 6-hydroxydopamine lesions of the lateral septum in the rat.

Tested the effect of local injections of 6-hydroxydopamine (6-OHDA [3 μg/1 μl]) into the lateral septum in a paradigm that leads to an energizing behavior, through a possible frustrative effect, induced by partial or total omission of reward in hungry adult male Sprague-Dawley rats. Biochemical assays in the septum showed that 6-OHDA reduced endogenous dopamine and, to a lesser extent, noradrenaline concentrations and left intact noncatecholaminergic neurons such as serotoninergic terminals. In a double straight alley, Ss were exposed to an acquisition phase, a partially reinforced phase, and an extinction phase. Ss with lesions ran faster for food than controls in the partial reinforcement or extinction situation. The 2 groups also behaved similarly after the 1st 6 trials of the extinction phase. When Ss were tested in a leverpress conditioning task, lesioned and control Ss learned this task equally well, both with respect to the number of leverpresses and the time to obtain a fixed number of food pellets. In the 1st 5 min following the omission of reward, the number of leverpresses increased more for the lesioned Ss than for controls, a difference that disappeared in the later stages of the test. Results indicate that the loss of septal dopaminergic innervation produces behavioral effects similar to those obtained after total destruction of the same areas by electrocoagulation. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat

Acetylcholinesterase (AChE, EC 3.1.1.7) was extracted from sheep platelets by successive homogenizations, yielding low-salt soluble (LSS), high-salt soluble (HSS) and detergent-soluble (DS) fractions. These accounted, respectively, for about 30%, 7% and 60% of total AChE activity. Applications of hydrophobic chromatography on phenyl-agarose to three solubilized fractions revealed that hydrophilic forms were almost exclusively located in the LSS fraction ( approximately 27% of total AChE), whereas most amphiphilic forms were present in DS extracts ( approximately 59% of total AChE), the remaining forms being distributed among aqueous soluble fractions. Enzyme molecular forms in the solubilized extracts were identified by centrifugation in 5-20% sucrose gradients containing Triton X-100 or Brij 97 to differentiate between hydrophilic or amphiphilic species. A predominance of hydrophilic dimeric forms ( approximately 22%), with small amounts of hydrophilic monomers (5%) and amphiphilic dimers and monomers (3%), was found in soluble AChE (LSS fraction). Amphiphilic AChE forms extracted in the HSS and DS fractions had a single peak in the sedimentation profiles with sedimentation coefficients of about 6S in gradients with Triton X-100; these were slightly shifted in the presence of Brij 97. After treatment with dithiothreitol, this molecular form solubilized in DS was converted to another molecular form with a lower sedimentation coefficient. Our results show that amphiphilic globular dimers are the dominant molecular form in sheep platelet AChE, suggesting a partial conversion of this membrane-bound form into soluble dimers and monomers, mainly with a hydrophilic character, through the action of either endogenous proteases and phospholipases or residual endogenous reducing agents.     

Drinking and Fos-immunoreactivity in rat brain induced by local injection of angiotensin I into the subfornical organ

Previous studies suggested that angiotensinergic stimulation in the subfornical organ (SFO) has effects on the anterior third ventricle (AV3V) region and the hypothalamus for dipsogenic response and vasopressin release. In this study, Angiotensin I (ANG I) was directly injected into the SFO and this stimulated drinking. Injection of ANG I into the SFO also induced Fos-immunoreactivity (Fos-ir) in the AV3V region and in the vasopressin neurons of the supraoptic and paraventricular nuclei (SON and PVN). Pretreatment of the SFO with either captopril, an ANG converting enzyme inhibitor, or losartan, an AT1 receptor antagonist, abolished both drinking and Fos-ir induced by ANG I. Water intake partially decreased ANG I-induced Fos-ir in the SON and PVN, but not in the other areas. These results indicate that there is an ANG converting system in the SFO and suggest that neurons in the AV3V region and vasopressin cells in the hypothalamus can be regulated by angiotensinergic components in the SFO.     

Effect of 6-hydroxydopamine injection into the arcuate hypothalamic nucleus on the osmotic release of vasopressin in conscious rats

The aim of the present study was to evaluate a role in vasopressin secretion of the catecholaminergic neurons, including the tuberohypophysial dopaminergic neurons situated in the arcuate hypothalamic nucleus. A neurotoxin, 6-hydroxydopamine (6 g/l), was injected locally into the arcuate nucleus and its effects on catecholamine levels of the hypothalamic tissue and the neurointermediate lobe, and on the plasma vasopressin concentrations before and during i.v. infusion (0.1 ml kg-1 min-1) of isotonic (0.15 mol/l) or hypertonic saline (2.5 mol/l), were examined in conscious rats. The infusion of hypertonic saline produced increases of plasma vasopressin 15 and 30 min later, accompanied by elevations of plasma osmolality, sodium, chloride and arterial pressure. The vasopressin response was potentiated markedly by the 6-hydroxydopamine injection performed 8 days before, which hardly affected the responses of the other variables. Histological examination indicated that the injection sites of 6-hydroxydopamine in those rats had been located in the area ranging from rostral to medial arcuate nucleus. The i.v. infusion of isotonic saline did not change plasma vasopressin, osmolality, sodium, chloride or arterial pressure, regardless of the presence or absence of pretreatment with 6-hydroxydopamine. It was confirmed that when 6-hydroxydopamine was injected into the arcuate nucleus region 8 days before, noradrenaline and adrenaline concentrations of the hypothalamic tissue containing the injection site were decreased remarkably, although we could not detect any significant alteration in the dopamine concentration of the hypothalamic tissue or the neurointermediate lobe. On the basis of these results, we concluded that catecholaminergic neurons in the arcuate nucleus may act to inhibit osmotic vasopressin secretion.     

Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3

Rats were exposed to either NO2 or O3 to determine whether nonciliated cells (Clara cells) could divide and differentiate into ciliated cells in the terminal bronchioles. Dividing cells were labeled with tritiated thymidine, visualized in the light and electron microscopes using autoradiographic techniques, and studied for up to 15 days after labeling. Electron microscopic autoradiography 1 hour after injection of tritiated thymidine showed that all labeled cells in the terminal bronchioles were nonciliated. However, 4 days after injection of tritiated thymidine, 67.8 per cent of the labeled cells were nonciliated and 32.2 per cent were ciliated. Light microscopic autoradiography showed that the new labeled ciliated cell population was stable for up to 15 days. These results indicate that nonciliated cells divide and the sister cells may form new ciliated and nonciliated cells. Thus, nonciliated cells can act as progenitor cells for the terminal bronchiolar epithelium.     

Repeated injection of GBR 12909, but not cocaine or WIN 35,065-2, into the ventral tegmental area induces behavioral sensitization

A role for the mesolimbic dopamine system in the development of behavioral sensitization to psychostimulants, such as cocaine and amphetamine, is well established. Previous reports have suggested that the ventral tegmental area (VTA) is involved in the initiation of, while the nucleus accumbens is in involved in the expression of behavioral sensitization. This hypothesis is supported in part, by studies which demonstrated that behavioral sensitization could be induced by repeated intra-VTA, but not intra-accumbal, administration of amphetamine. The present studies were designed to determine whether repeated intra-VTA cocaine would similarly induce behavioral sensitization. Rats receiving four daily injections of cocaine (1.5, 5 or 15 nmol/side) into the VTA did not show a sensitized behavioral response when challenged with cocaine (15 mg/kg, ip) 1 week later. In contrast to this, repeated injection of the specific dopamine reuptake inhibitor, GBR 12909 (15 nmol/side) produced behavioral sensitization to a challenge injection of cocaine. Repeated injections of the cocaine analog WIN 35,065-2 did not induce behavioral sensitization to cocaine, suggesting that the local anesthetic properties of cocaine were not responsible for the inability of intra-VTA cocaine to induce sensitization. In summary, the data suggest that sensitization to cocaine may involve mechanisms different from amphetamine.     

Hyperreactivity, muricide, and intraspecific aggression in the rat produced by infusion of local anesthetic into the lateral septum or surroundng areas.

Intracranial infusions of a local anesthetic (lidocaine, 2%) were made bilaterally (4 μl over 20 min) through permanently implanted cannulas ending in the lateral septum or adjacent areas in 167 male hooded rats. Increases in irritability and reactivity to the experimenter, muricide, and intermale aggression were produced by injections into the lateral septum and the region ventral to it. The increase in reactivity and interanimal aggression occurred in varying degrees and were independent of one another, but intermale aggression occurred only in Ss showing muricide. The most effective site for eliciting the entire spectrum of aggressive behaviors was the region ventral to the anterior septum. The region ventral to the posterior septum tended to produce a high incidence of muricide with only modest increases in reactivity. No changes in behavior were noted with infusions into the medial septum or the medial forebrain bundle/lateral preoptic area ventrolateral to the septum. It is suggested that the hyperreactivity and irritability may be related to hyperdefensiveness and that muricide and intermale aggression are points on a continuum of interanimal aggressiveness. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)