Integrated cardiovascular function in the conscious streptozotocin-diabetic deoxycorticosterone-acetate-hypertensive rats

Blood pressure, heart rate, and left ventricular function were measured in conscious diabetic Sprague-Dawley rats subjected to 5 weeks of deoxycorticosterone acetate (DOCA) treatment which was started 1 week following intravenous injection of streptozotocin (STZ) (60 mg/kg) to induce diabetes mellitus. It was found that chronic administration of DOCA in nondiabetic animals caused an increase in blood pressure and functional parameters of left ventricle, and a decrease in heart rate and plasma insulin levels. Normotensive diabetic rats exhibited hyperglycemia, hypoinsulinemia, and a lower body weight as compared with control animals but did not show significant abnormalities in cardiovascular function. DOCA-hypertensive STZ-diabetic rats had similar hyperglycemia, milder hypoinsulinemia, and a significantly lower rate of left ventricular relaxation and systolic blood pressure compared with the nondiabetic DOCA-hypertensive animals. It is concluded that the addition of DOCA hypertension to intact 6-week STZ-diabetic Sprague-Dawley rats results in the occurrence of cardiac dysfunction.     

Effects of proposed treatments for cocaine addiction on hemodynamic responsiveness to cocaine in conscious rats

Several agents may treat cocaine addiction and toxicity including bromocriptine, desipramine, GBR 12909 [1-(2-(bis(4-fluorphenyl)-methoxy)-ethyl)-4-(3-phenyl-propyl) piperazine], diazepam, buprenorphine and dizocilpine. In this study, we sought to determine whether these specific therapeutic agents alter cardiovascular responses to cocaine in conscious rats. Arterial pressure responses to cocaine (5 mg/kg, i.v.) were similar in all rats whereas cardiac output responses varied widely. In 26 of 33 rats (named vascular responders), cocaine induced a decrease in cardiac output of 8% or more. The remaining rats with little change or an increase in cardiac output were classified as mixed responders. Pretreatment with bromocriptine (0.1 mg/kg) or desipramine (1 mg/kg) increased cardiac output in mixed responders and increased systemic vascular resistance in vascular responders similar to the differential effects noted with cocaine. GBR 12909 (0.5-10 mg/kg) elicited a decrease in cardiac output at higher doses. Diazepam (0.1 and 0.5 mg/kg) had small, short-lasting effects on cardiovascular parameters. Buprenorphine (0.3 mg/kg) or the NMDA (N-methyl-D-aspartic acid) receptor antagonist, dizocilpine (0.05 mg/kg), increased arterial pressure, heart rate and cardiac output in vascular responders. Bromocriptine and desipramine prevented the difference in cardiac output responses in vascular and mixed responders by reducing the cocaine-induced decrease in cardiac output in vascular responders. Pretreatment with GBR 12909 (1 mg/kg) had little effect on cardiovascular responses to cocaine except to depress the increase in cardiac output noted in mixed responders. Buprenorphine selectively enhanced the increase in systemic vascular resistance whereas dizocilpine enhanced the pressor response. These data suggest that several treatment regimens for cocaine addiction alter the cardiovascular responses to cocaine and that dopamine D2 receptor activation may be necessary for the decrease in cardiac output noted in vascular responders.     

Long-term cardiovascular role of nitric oxide in conscious rats

Twenty-eight non-allergic subjects suffering from mono- and bilateral chronic nasal respiratory obstruction underwent investigation employing routine semeiological examination. The real cause of the obstruction, however, was not ascertained. The subjects underwent nasal endoscopy employing rigid fiberoptics and, on the grounds of the findings, a cat scan of the nasal fossae in coronal projection, was made. The results of the study revealed involvement of the middle meatal area in 63% of bilateral nasal obstructions (B.N.O.) and in 77.7% of the monolateral obstructions (M.N.O.). Choanal pathology was evident in 21% of the B.N.O., while isolated upper and posterior deviations of the septum were present in 23.6% of the B.N.O. and in 22.5% of the M.N.O. Meatal involvement was due to the presence of anatomic changes of the middle turbinate (m.t.) such as concha bullosa, paradoxical deviation of the m.t. and of the uncinate process. Moreover, small "mucosal polyps" were also noticed in this meatal area. Cat scans, performed on 18 of these 28 patients, confirmed and defined meatal alterations found with endoscopy in 16 cases. In the remaining 2 cases, cat scans showed a thickening of the mucosal+bony tissues of the m.t. The Authors did not consider CT necessary in 10 subjects in that endoscopy sufficed in explaining obstruction symptoms.     

The effects of acute pretreatment with high-dose memantine on the cardiovascular and behavioral effects of cocaine in humans.

This study examined the acute effects of pretreatment with high-dose memantine, an N-methyl-D-aspartate antagonist, on the effects of cocaine in humans. Six African American men completed this laboratory study, in which, following pretreatment with memantine (0 or 60 mg), they had 5 opportunities to smoke cocaine base (0, 12, 25, or 50 mg) or receive an alternative reinforcer ($5.00 merchandise voucher). Cocaine alone produced the well-documented dose-dependent increases in cardiovascular activity and ratings of positive mood. Maximal systolic blood pressure was elevated during memantine pretreatment days. Peak ratings of "I feel stimulated" and "I feel anxious" were also higher with memantine pretreatment. However, memantine pretreatment did not alter the choice to self-administer cocaine. These data suggest that memantine pretreatment may not be helpful in the treatment of cocaine dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural mechanisms of tolerance to the effects of cocaine

Chronic use of cocaine in high doses can produce tolerance as assessed by various behavioral, neurochemical, cellular and molecular measures in specific brain regions. Tolerance to cocaine is indicated by drug discrimination and intracranial self-stimulation models, which show the development of tolerance after approximately 1 week of frequent cocaine treatment, with recovery after a similar period of cocaine abstinence. Tolerance to the reinforcing properties of cocaine depends on dose, duration and frequency of cocaine self-administered by experimental animal or human subjects. The mechanism underlying this effect may involve an absolute or relative attenuation of dopamine response to cocaine challenge after frequent or repeated treatment in the nucleus accumbens (NAc). Similarly, afferent and efferent NAc circuits exhibit reduced metabolic activity, which lasts throughout the early period of withdrawal following repeated treatment. Attenuation of immediate early gene response also occurs, which might be related to a functional desensitization of dopamine D1-like receptors. Furthermore, intracellular adaptive responses to chronic cocaine exposure induce striatal dynorphin expression decreasing the behavioral potency of subsequent drug treatment. Thus, a combination of various pharmacodynamic mechanisms and the attenuation of dopamine response induced by sufficient dose, duration and frequency of cocaine exposure ultimately invoke the transient development of tolerance to the reinforcing effects of cocaine.     

Respiratory and cardiovascular effects of prostaglandins in the conscious guinea pig

A technique to assess respiratory and cardiovascular effects of prostaglandins (PGs) in conscious guinea pigs was developed. Animals were placed in a plethysmograph and tidal volume, airflow, and heart rate were recorded. In addition, blood pressure and/or pleural pressure were obtained. Some experiments involved the use of a pulmonary calculator that processed the appropriate pulmonary signal and provided on-line readout of dynamic compliance and airway resistance. Aerosolized antagonists were evaluated for their ability to block responses to aerosolized histamine. We found the relative antagonistic potencies of PGE1, PGE2, isoproterenol, and salbutamol to be 5.5, 2.3, 1 and 0.2, respectively. Aerosolized PGE1 and PGE2 but not PGF2alpha given prior to histamine caused decreases in tidal volume, airflow and heart rate. These effects were not seen in animals that were prepared for measurements involving invasive surgical techniques. The aerosolized PGE2 induced tidal volume changes were not prevented by pretreatment with salbutamol, chlorpheniramine, atropine or hexamethonium, though the latter two drugs inhibited the fall in heart rate. We suggest that the bradycardia following aerosolized PGE2 administration may originate from airway irritant receptors. The results validate use of our methods for the assessment of responses to bronchoactive agents under physiological conditions.     

Systemic and coronary hemodynamic effects of repetitive cocaine administration in conscious dogs

The cardiovascular actions of cocaine are complex, and previous studies suggest that tachyphylaxis to the positive chronotropic and pressor effects of cocaine may develop after repetitive administration. We examined changes in systemic and coronary hemodynamics when single or multiple doses of intravenous (i.v.) cocaine were administered to conscious dogs. Dogs were chronically instrumented for measurement of aortic blood pressure (BP) and left ventricular pressure (LVP), LV dP/dtmax and dP/dt50, subendocardial segment length (%SS), diastolic coronary blood flow (CBF) velocity, and cardiac output (CO). Myocardial oxygen consumption was estimated by the pressure-work index (PWI). In one series of experiments, a single dose of cocaine (0.1, 0.2, 0.4, 0.8, or 1.6 mg/kg) was administered on 5 consecutive days in random fashion and peak changes in systemic and coronary hemodynamics were recorded. These doses were then randomly repeated in a second group of experiments with a 1-h interval between doses on the same day. Peak and steady-state changes in cardiovascular variables were recorded within and between each dose, respectively. In other experiments, higher doses of cocaine (0.8 or 1.6 mg/kg; separate groups) were administered four times at 1-h intervals in the same dogs and peak and steady-state changes in hemodynamics were determined. Cocaine caused dose-related increases in heart rate (HR), mean arterial pressure (MAP), LV systolic pressure (LVSP) and end-diastolic pressure (LVEDP), PWI, CO, and diastolic coronary vascular resistance and decreases in %SS when administered on different days. Cocaine also caused significant increases in baseline HR, MAP, LVSP, and PWI between doses given on the same day at 1-h intervals, but the absolute value of the peak response to cocaine of these hemodynamic parameters was independent of dosing regimen. These results were confirmed when we administered four doses of 0.8 mg/kg cocaine at 1-h intervals. The results indicate that baseline changes in systemic hemodynamic variables are a predominant feature of repetitive administration of lower doses of cocaine (< or = 0.8 mg/kg), but administration of higher doses of cocaine (> or = 8 mg/kg) at 1-h intervals caused tachyphylaxis to the hypertensive actions and myocardial oxygen consumption effects of cocaine.     

Autonomic components of the cardiovascular responses to an acoustic startle stimulus in rats

The Afa-family repetitive sequences were isolated from barley (Hordeum vulgare, 2n = 14) and cloned as pHvA14. This sequence distinguished each barely chromosome by in situ hybridization. Double color fluorescence in situ hybridization using pHvA14 and 5S rDNA or HvRT-family sequence (subtelomeric sequence of barley) allocated individual barley chromosomes showing a specific pattern of pHvA14 to chromosome 1H to 7H. As the case of the D genome chromosomes of Aegilops squarrosa and common wheat (Triticum aestivum) hybridized by its Afa-family sequences, the signals of pHvA14 in barley chromosomes tended to appear in the distal regions that do not carry many chromosome band markers. In the telomeric regions these signals always placed in more proximal portions than those of HvRT-family. Based on the distribution patterns of Afa-family sequences in the chromosomes of barley and D genome chromosomes of wheat, we discuss a possible mechanism of amplification of the repetitive sequences during the evolution of Triticeae. In addition, we show here that HvRT-family also could be used to distinguish individual barley chromosomes from the patterns of in situ hybridization.     

Interrelationship of cardiovascular effects, plasma levels of nicorandil, and vascular cGMP formation in conscious rats

OBJECTIVE: To determine the reproducibility of duplex Doppler waveform analysis and fetal cardiac interventricular septal thickness measurement and to compare these parameters in matched pregnancies with and without well-controlled maternal Type 1 diabetes at 18-20 weeks of gestation. DESIGN: A prospective blind twin cohort study and a blinded inter-observer and intra-observer agreement study. SETTING: A tertiary referral prenatal diagnostic unit within a university hospital. RESULTS: Good inter- and intra-observer agreement was found for the measurement of transvalvular peak flow velocities and the duration of ventricular ejection in the fetal heart. Inter-observer agreement for aortic flow acceleration rate was poor. M-mode measurement of interventricular septal thickness showed moderate reproducibility. The mean (SD) width of the interventricular septum in the fetuses of well controlled diabetic women was 2 1 mm (0.2 mm), and was significantly greater (P=0.01) when compared with the corresponding value in matched controls [1.9 mm (0.2 mm)]. No cardiac functional differences were evident. CONCLUSIONS: On-screen video analysis of Doppler cardiac flow waveforms and M-mode measurement of intraventricular septal thickness demonstrated good reproducibility. The fetuses of well controlled diabetic pregnancies demonstrated signs of altered cardiac morphology early in pregnancy, before any evident alterations in cardiac function.     

Hypotensive effects of peptide T in conscious rats

1. The present study investigated the effects of peptide T on mean arterial blood pressure (MAP) in conscious normotensive Sprague-Dawley (SD) rats, spontaneously hypertensive rats (SHR) and two-kidney one-clip (2K1C) hypertensive rats. 2. Peptide T was infused via the left jugular vein at a rate of 1 mg/kg per h in SD, SHR and 2K1C rats and then at doses of 0.1, 0.25, 0.5, 1 and 5 mg/kg per h in SHR, with 0.9% saline as a sham control in SHR and 2K1C. Mean arterial pressure was measured directly before, during and after infusion. 3. Peptide T (1 mg/kg per h) decreased blood pressure in both SHR (P < 0.01) and 2K1C (P < 0.05). In normotensive SD rats the fall in MAP approached statistical significance (P = 0.06). The effect of peptide T was not significantly different in normotensive compared with hypertensive rats. Saline infusion had no effect. The blood pressure lowering effect of peptide T appeared to be dose-dependent in SHR.     

The effects of memantine on the subjective, reinforcing and cardiovascular effects of cocaine in humans

Eight male frequent cocaine smokers participated in a 44- to 47-day inpatient and outpatient study to assess the effects of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, memantine, on cocaine self-administration, subjective effects, and psychomotor performance. Participants were maintained on memantine (0 and 20 mg daily) for 7-10 days prior to laboratory testing, using a double-blind crossover design. Under each medication condition, participants smoked four doses of cocaine base (0, 12, 25 and 50 mg), and were subsequently given five opportunities, 14 min apart, to self-administer that dose of cocaine or receive a merchandise voucher ($5.00). Each cocaine dose was tested twice under each medication condition, and the order of medication condition and cocaine dose was systematically varied. Vital signs were recorded every 2 min, and subjective effects were assessed at baseline and after each cocaine or voucher delivery. In addition, psychomotor performance was assessed before and after each self-administration session. Memantine maintenance was not associated with changes in psychomotor performance or the number of cocaine doses chosen each session. Memantine maintenance was, however, associated with significant increases in some subjective effects of cocaine, including ratings of 'good drug effect', 'high', 'potency', 'quality', and street value. These data suggest that NMDA antagonists may have limited usefulness as treatment medications for cocaine abuse.     

Intravenous cocaine induces platelet activation in the conscious dog

BACKGROUND: Cocaine consumption has been associated with thrombosis of coronary and peripheral arteries. Since cocaine has been found to induce platelet activation in vitro, we sought to establish whether cocaine induced platelet activation in vivo. METHODS AND RESULTS: Chronically instrumented, conscious dogs were infused with cocaine (1 mg/kg), norepinephrine (0.2 to 0.4 mg/kg), or saline intravenously over 1 minute. Activated canine platelets were identified in whole blood collected from an indwelling aortic catheter by flow cytometric detection of the binding of a monoclonal antibody directed against the activation-dependent antigen P-selectin. Infusion of cocaine resulted in an elevation of mean arterial pressure (91 +/- 3 to 128 +/- 7 mm Hg [P < .01]) and heart rate (87 +/- 9 to 125 +/- 11 beats per minute [P < .01]). A similar change (P = NS) in mean arterial pressure followed norepinephrine infusion (100 +/- 5 to 137 +/- 13 mm Hg [P < .04]), whereas saline infusion had no effect. Cocaine resulted in a substantial but delayed increase in platelet P-selectin expression (14 +/- 7% [P < .08], 31 +/- 12% [P < .04], and 55 +/- 22% [P < .04] at 17, 22, and 27 minutes after drug infusion, respectively). The magnitude of this increase was similar to that found in blood treated ex vivo with the agonists ADP or PAF (23 +/- 7% and 53 +/- 15%, respectively). No significant increase in P-selectin expression was detected in the blood of animals that received norepinephrine or saline. Serum cocaine concentrations were highest immediately after infusion (538 +/- 55 ng/mL at 2 minutes) but declined rapidly (185 +/- 22 and 110 +/- 25 ng/mL at 17 and 32 minutes after infusion); in contrast, the increase in benzoylecgonine concentrations was delayed (from < 25 ng/mL in all but one animal [34 ng/mL] at 2 minutes to 46 +/- 4 and 71 +/- 11 ng/mL at 17 and 32 minutes, respectively, after infusion). CONCLUSIONS: Intravenous cocaine induces activation of individual circulating platelets; this effect is not reproduced by infusion of norepinephrine at doses sufficient to exert similar hemodynamic effects. The delay in detection of activated platelets after treatment with cocaine may result from the adhesion and subsequent detachment of activated platelets; alternatively, cocaine metabolites, rather than the drug itself, may induce platelet activation.     

Autonomic assessment of cardiovascular disease

Port wine stains (PWS) can lead to considerable emotional distress. The present study evaluated a) the coping with illness, the quality of life and the body image of patients with PWS and b) the effects of dye laser treatment on psychosocial parameters. Seventy PWS patients undergoing treatment with the flashlamp-pumped pulsed dye laser (FPDL) were assessed with questionnaires regarding coping with skin disease, quality of life and body image. Major clinical criterium was the lightening of PWS under treatment. PWS patients showed significant social phobia and avoidance similar to patient suffering from chronic skin diseases. The anxiety correlated with size and darkness of the PWS. In terms of helplessness and depressive mood, PWS patients were less affected than the comparison group. Also, PWS patients had reductions in quality of life and in body image. The coping strategies had a differential effect on the body image. Since there is a correlation between lightening of the PWS and reduction of emotional distress, FDPL therapy can be considered an effective treatment of PWS also in psychosocial terms.     

Cardiovascular and renal effects of hypoxia in conscious carotid body-denervated rats

The contribution of peripheral arterial chemoreceptors to cardiovascular and renal responses to acute hypocapnic hypoxia is currently not well understood. We compared the effects of normobaric hypoxia on mean arterial blood pressure (MABP), heart rate, glomerular filtration rate (GFR), renal blood flow (RBF), and renal volume and electrolyte excretion in conscious unilaterally nephrectomized carotid body-denervated (n = 10) and sham-operated (n = 10) control rats. Thirty minutes of normobaric hypoxia (12.5% O2) resulted in significant reductions in arterial PO2 and PCO2 as well as decreases in MABP, GFR, RBF, and renal sodium, potassium, and water excretion. These effects occurred more rapidly and/or were significantly more pronounced in carotid body-denervated than in sham-operated rats. These data indicate that moderate acute hypocapnic hypoxia has profound effects on systemic and renal hemodynamics as well as on renal excretory function in conscious rats. We conclude that stimulation of the peripheral arterial chemoreceptors can partially offset the hypoxia-induced decreases in MABP, RBF, GFR, urine flow, and urinary sodium and potassium excretion, thereby helping to maintain cardiovascular as well as fluid and electrolyte homeostasis.     

State-dependent stimulus control: cuing attributes of acute cocaine rebound in rats

General and rapid methods were developed for determining the extent of non-covalent binding between small molecules and proteins, using the model system of human cytomegalovirus protease and several drug candidates which inhibit the protease by non-covalently binding to it. The assay was performed by off-line coupling of size-exclusion methods with mass spectrometry in the following manner. The protease and inhibitor were incubated together under native conditions and then subjected to separation based on size, by use of a spin column (gel permeation chromatography) and/or a microconcentrator (ultrafiltration). The spin column selectively passed the high molecular mass (M(r)) protease and trapped low M(r) molecules. Alternatively, the microconcentrator passed low M(r) molecules and retained the protease. If the inhibitor bound non-covalently to the protease, both the inhibitor and protease passed through the spin column (or were retained by the microconcentrator). Electrospray ionization mass spectrometry was used to assay the spin column eluate (or the microconcentrator retentate) and to characterize the amounts of protease and inhibitor based on known standards. An advantage of these techniques is that a mixture containing inhibitors can be analyzed in the presence of the protease, and inhibitors with the greatest binding affinity can be identified. Non-covalent binding specificity was demonstrated using spin columns by comparing the binding affinity of inhibitors using several mutants of cytomegalovirus protease. The techniques described are applicable to the rapid screening of compound libraries for selecting substances which bind non-covalently to a known protein.     

Cardiovascular effects of oxymetazoline and UK14,304 in conscious and pithed rats

Relatively selective alpha 2-adrenoceptor agonists have proven useful in a variety of therapeutic situations including hypertension, glaucoma and withdrawal from opiate addiction. In particular, oxymetazoline (OXY) and UK14,304 (UK) have been used in subclassifying alpha 2-adrenoceptors and imidazoline receptors. We evaluated the cardiovascular effects of OXY and UK in conscious and pithed rats in the presence and absence of efaroxan (EFA), idazoxan (IDA) and rauwolscine (RAU). Both OXY or UK (1, 5 and 10 micrograms/kg, i.v.) increased blood pressure (BP) and reduced heart rate (HR) in conscious rats. In pithed rats, OXY and UK each increased BP to a greater extent than that observed in conscious rats, but HR was not affected. BP increases following sympathetic nerve stimulation in the pithed rats were not affected by OXY but were reduced by UK at 0.1 Hz and 0.3 Hz. HR responses to nerve stimulation in pithed rats were reduced after OXY at all frequencies, but only at 0.1 Hz following UK. EFA, IDA and RAU inhibited the pressor responses of UK, with EFA being most potent. OXY-induced pressor responses were inhibited by all three antagonists, RAU being the least potent. HR responses to either OXY or UK were not affected by the antagonists. Taken together, the data suggest that: 1) alpha 2-adrenoceptors contribute less to the vascular response to OXY than to UK based upon the antagonistic effect of RAU; 2) prejunctional I1 receptors maybe more prevalent in the heart than in vascular tissue based upon the response to OXY in pithed rats. Thus, the heterogeneity among receptors mediating cardiac and vascular responses are complex.     

Prenatal exposure to cocaine: effects on aggression in Sprague-Dawley rats

Social/aggressive behavior in adult rat offspring (beginning at postnatal Day 180) prenatally exposed to saline, cocaine, or amfonelic acid (AFA) was examined. Pregnant rats received injections of 15 mg/kg of cocaine, or 0.9% saline twice daily, s.c., or on 2 consecutive days at 4-day intervals, or 1.5 mg/kg amfonelic acid daily throughout gestational Days 1-20. Frequency, duration, and latency of 11 social/aggressive behaviors were recorded for two 15-min sessions during which a smaller male intruder replaced an ovariectomized female in the resident's home cage. Subjects received a s.c. saline injection before Session 1 and 2.0 mg/kg of gepirone, a 5HT1a partial agonist, prior to Session 2. Prenatal cocaine treatment resulted in alterations of aggressive behavior. Aggressive behavior was reduced by gepirone in all groups but to a lesser extent in the AFA group.     

Reflex cardiovascular changes with veratridine in the conscious dog

The present study was undertaken to examine the reflex responses of activation of cardiac sensory receptors in the conscious dog. Intracoronary (left circumflex coronary artery) injection of veratridine (0.10 micrograms/kg) reduced mean arterial pressure (-40 mmHg, P less than 0.05), heart rate (-34 beats/min, P less than 0.05), and maximum rate of rise of left ventricular pressure (LV dP/dtmax) (-419 mmHg/s, P less than 0.05). Bilateral cervical vagal cold block (BVB) eliminated the depressor and bradycardic responses of veratridine. BVB not only eliminated the negative inotropic response to veratridine but reversed it to a positive inotropic response (LV dP/dtmax increased 313 +/- 76 mmHg/s). Ganglionic blockade abolished all effects of veratridine. The bradycardia and negative inotropic effects caused by veratridine were attenuated by either atropine or metoprolol and completely eliminated by the combination of the two antagonists. Veratridine also produced a decrease in renal artery blood flow but had no effect on renal vascular resistance. In contrast, iliac blood flow was increased with veratridine, and this, combined with the depressor effect, resulted in a decrease in iliac vascular resistance (-37%), P less than 0.05). BVB abolished the changes in renal and iliac blood flow or resistance caused by veratridine. The results indicate that activation of cardiac receptors in the conscious dog elicits inhibitory reflexes to the heart and peripheral circulation that are mediated by vagal afferents. After vagotomy, veratridine elicited a reflex positive inotropic response, which may have resulted from activation of cardiac sympathetic afferent fibers.     

Effects of acute and delayed effects of prior chronic cocaine administration on regional rates of cerebral protein synthesis in rats

Single or repeated treatments with cocaine (15 mg/kg, i.p.) in rats modify rates of local cerebral protein synthesis (ICPSleu) measured with the [1-14C]leucine method. A single dose of cocaine to naive rats reduced ICPSleu by about 10% throughout the brain; the most statistically significant reduction was in the nucleus accumbens, shell portion (P = .0003). A comparable dose of cocaine administered acutely after 1 wk of daily cocaine injections had no effects on ICPSleu. Delayed effects of prior chronic cocaine treatment were studied in experiments in which one rat of each pair received injections with saline for 8 days and the other cocaine, and on the 15th day ICPSleu was measured. In these experiments delayed effects of the chronic cocaine treatment were observed; in the cocaine-treated rats ICPSleu was significantly increased in selective brain regions, i.e., prefrontal and primary olfactory cortex (P < .006). These results suggest that acute effects of a single dose of cocaine and residual effects of chronic cocaine treatment on ICPSleu are distinctly different and occur in different regions of the brain.     

Cerebrospinal fluid pressure changes after acute carbon monoxide poisoning and therapeutic effects of normobaric and hyperbaric oxygen in conscious rats

This study on conscious rats with occluded left carotid artery investigates the influence of cerebral edema after acute carbon monoxide (CO) poisoning on cerebrospinal fluid pressure (CSFp) and evaluates the therapeutic effectiveness of normobaric oxygen (NBO2) and hyperbaric oxygen (HBO2). The CSFp was continuously recorded via a cannula placed in the left cerebral ventricle before, during, and for up to 6 h after exposure to 0.27% CO for 1 h. A non-sustained small increase in the CSFp and identical degrees of hypoxemia, hypocapnia, arterial hypotension, and acidosis were found during the exposure in all rats. After the CO exposure, all non-edema control rats without carotid artery ligation (n = 7) recovered completely with normal CSFp, behavior, and brain water content. All untreated (n = 7) and NBO2-treated rats (n = 7) developed a severely increased CSFp (> 50 mmHg) with neurologic motor dysfunction, and died of a severely increased CSFp (> 100 mmHg) with considerable cerebellar herniation. Except in one rat, the CSFp did not reach a dangerous level (> 25 mmHg) after the HBO2 session (300 kPa O2 for 1 h, beginning at 20 min post CO). All HBO-treated rats (n = 7) survived with less neurologic motor dysfunction and less left hemispheric edema than those in untreated and NBO2-treated rats. The results demonstrated that the increase in the CSFp was related to the left hemispheric edema, and that the cerebellar herniation was the predominant cause of death after the CO exposure. HBO2, but not NBO2, prevented the severe increase in the CSFp and thus saved the life after the CO exposure.