The relation of initial alcohol experiences to current alcohol consumption in a college population.

Male and female undergraduate college students were surveyed to examine whether age and circumstances of initial taste and intoxication experiences with alcohol would be predictive of current alcohol usage. Age of initiation, nature of the experience (pleasant vs unpleasant), social setting and type of beverage were examined. Only age of initial experience was found to be minimally predictive of subsequent heavier alcohol use. The negative effects of early experiences with alcohol were predictive for abstinence in both sexes, but did not differentiate between moderate and heavy alcohol users in either.

Adjunctive alcohol drinking in humans.

In an attempt to validate the animal model of adjunctive ethanol drinking in people, human subjects were allowed access to ad lib beer while playing a game that delivered monetary reinforcements on a FI schedule. Subjects exposed to a longer FI schedule drank significantly more than those exposed to a shorter schedule, confirming the prediction made by the animal model. A pattern of ingestion characteristic of adjunctive drinking was also observed in the longer FI condition, providing evidence that ethanol drinking in humans can be schedule-induced.

Dose dependent radiation-induced hypotension in the canine.

Radiation-induced early transient incapacitation (ETI) is often accompanied by severe systemic hypotension. However, postradiation hypotension does not occur with equal frequency in all species and is not reported with consistency in the canine. In an attempt to clarify the differences in reported canine postradiation blood pressures, canine systemic blood pressures were determined both before and after exposure to gamma radiation of either 80 Gy or 100 Gy. Data obtained from six sham-radiated beagles and 12 radiated beagles indicated that 100 Gy, whole-body, gamma radiation produced a decrease in systemic mean blood pressure while 80 Gy, whole-body, gamma radiation did not. Analysis of this data could be consistent with a quantal response to a gamma radiation dose between 80 Gy and 100 Gy.

Disodium cromoglycate, a mast-cell stabilizer, alters postradiation regional cerebral blood flow in primates.

Early transient incapacitation (ETI) is the complete cessation of performance during the first 30 min after radiation exposure, and performance decrement (PD) is a reduction in performance at the same time. Supralethal doses of radiation have been shown to produce a marked decrease in regional cerebral blood flow in primates concurrent with systemic hypotension and a dramatic release of mast-cell histamine. In an attempt to elucidate mechanisms underlying the radiation-induced ETI/PD phenomena and the postradiation decrease in cerebral blood flow, primates were given the mast-cell stabilizers disodium cromoglycate (DSCG) or BRL 22321 (Beecham Pharmaceuticals, Research Division) before exposure to 100 Gy whole-body gamma radiation. Hypothalamic and cortical blood flows were measured by hydrogen clearance, before and after radiation exposure. Systemic blood pressures were determined simultaneously. The data indicated that DSCG was successful in diminishing postradiation decrease in cerebral blood flow. Irradiated animals pretreated with DSCG, showed only a 10% decrease in hypothalamic blood flow 60 min postradiation, while untreated, irradiated animals showed a 57% decrease. The cortical blood flow of DSCG treated, irradiated animals showed a triphasic response, with a decrease of 38% at 10 min postradiation, then a rise to 1% below baseline at 20 min, followed by a fall to 42% below baseline by 50 min postradiation. In contrast, the untreated, irradiated animals showed a steady decrease in cortical blood flow to 79% below baseline by 50 min postradiation. There was no significant difference in blood-pressure response between the treated and untreated, irradiated animals. Systemic blood pressure showed a 60% decrease at 10 min postradiation, falling to a 71% decrease by 60 min. The effects of BRL 22321 in altering postradiation blood flow in the cerebral cortex and hypothalamus were intermediate between the irradiated controls and those pretreated with DSCG, but were not considered to be significant at the concentration employed. The overall results of this study indicate that the postradiation decrease in regional cerebral blood flow may be partially alleviated by treatment with a mast-cell stabilizer.

Schedule-induced drinking in humans: a potential factor in excessive alcohol use.

The timed delivery of monetary reinforcement by a computer-controlled slot machine altered the amount of fluid drunk adjunctively by human subjects. In separate experiments, subjects were allowed access to one of three fluids, water, non-alcoholic beer, or alcoholic beer, while receiving monetary reinforcement from the slot machine on one of two Fixed-Interval schedules (FI30 s or FI90 s). The largest difference in intake between the two schedule conditions occurred when water was the fluid available, but a similar trend in consumption was observed in the other studies. Greater consumption occurred when reinforcement was presented on the FI90-s schedule, which was predicted from previous studies using animals. The possible interaction of schedule-induced drinking with other variables known to influence human alcohol consumption is discussed.

Antihistamines block radiation-induced increased intestinal blood flow in canines.

Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H1 and H2 histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H1 and H2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systemic plasma histamine levels were determined simultaneously. Data obtained indicated that the H1 and H2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure.

Oral ethanol self-administration in the rat: effect of naloxone.

Rats responding on a two lever concurrent for ethanol and water, were injected with 5, 10, or 20 mg/kg naloxone hydrochloride 30 min prior to a 30 min session. Only the 20 mg/kg dose had any effect, a decrease in responding for ethanol of up to 50% compared to saline control injection sessions. There were no systematic effects upon water responding. An additional study using sucrose and water as the fluid concurrently available failed to find any effects of naloxone on sucrose responding at the same doses. The effect upon ethanol responding was found not to resemble a pattern of extinction, but rather was best described as a general overall reduction in responding. The relation of these findings to the direct involvement of the endogenous opiate system in ethanol reinforcement is discussed.

Canine postradiation histamine levels and subsequent response to Compound 48/80.

Radiation-induced hypotension in the beagle is accompanied by increased intestinal blood flow (IBF) and hematocrit (HCT). This study was performed to correlate these radiation-induced changes with plasma histamine (PH) levels following radiation. The histamine (H) levels were monitored in the systemic arterial circulation (SA) and the hepatic portal vein (HPV) before and after radiation. To examine the effect of radiation on the mobilization of total body H stores, Compound 48/80 was given I.V., and H responses were monitored in both control and radiated animals. Data obtained indicated that 100 Gy, whole-body, gamma-radiation produced a decrease in systemic mean blood pressure (BP), an increase in IBF and an increase in HCT. Concurrently, the mean PH/SA values increased and the PH/HPV levels decreased. Compound 48/80 produced a marked increase in PH levels in both control and radiated animals; however, the levels found in the radiated animals were consistently lower than those in the controls, although not statistically different. This implies that H may mediate these observed intestinal responses and that the mobility of histamine is decreased in radiated animals.

Canine postradiation plasma glucose variations.

One of the observations of endotoxic or septic shock in canines is the report of concurrent hypoglycemia. Canines exposed to supralethal gamma radiation also develop acute systemic hypotension. This study was performed in order to determine if hypoglycemia develops in the canine concurrent with radiation-induced hypotension. Systemic arterial mean blood pressure (MBP) was measured via femoral arterial catheter. Blood for plasma glucose determinations was obtained from the systemic arterial circulation at the level of the abdominal aorta and from the hepatic portal vein. Plasma glucose levels were determined on a Beckman Glucose Analyzer which employs the enzymatic reaction of beta-D-glucose and oxygen. Glucose levels and MBP were monitored for one hour before and for one hour after exposure to 100 Gy, whole-body, gamma radiation or sham radiation for the control animals. Concurrent with postradiation hypotension, we measured a significant decrease in plasma glucose levels in both the systemic arterial circulation and in the hepatic portal vein. Arterial glucose levels in the sham radiated animals showed a slight rise two minutes after sham radiation, falling back to pretreatment, base line levels four minutes later and remaining at that level for the remainder of the hour. Arterial levels in the radiated animals showed a sharp decline two minutes postradiation, falling even further to twenty percent below preradiation levels by one hour postradiation. Venous blood glucose levels in sham radiated animals showed an initial increase and a gradual decrease to five percent below pretreatment base line levels; while glucose levels in radiated animals showed an immediate postradiation decrease continuing to twenty percent below preradiation levels by one hour postradiation. These findings suggest impaired hepatic gluconeogenesis, resulting in postradiation hypoglycemia.

Acute post-irradiation canine intestinal blood flow.

Radiation-induced early transient incapacitation (ETI) is accompanied by severe systemic hypotension, during which arterial blood pressure often decreases to less than 50 per cent of normal. One haemodynamic compensatory mechanism is increased peripheral resistance due to vasoconstriction. This vasoconstriction in the small intestine of dogs is disproportionately increased during haemorrhagic or endotoxic shock, and intestinal ischaemia is frequent. In an attempt to elucidate mechanisms underlying radiation-induced ETI and the gastrointestinal radiation syndrome, canine intestinal submucosal blood flow was measured by the hydrogen polarographic technique, both before and after exposure to gamma radiation. Systemic blood pressures, blood gases and haematocrits were determined simultaneously. Data obtained from 12 sham-irradiated dogs and 12 irradiated dogs indicated that 90 Gy, whole-body, gamma radiation produced a 31 per cent decrease in systemic mean blood pressure beginning within 20 min post-irradiation and lasting for at least 90 min. However, the intestinal submucosal blood flow did not decrease as anticipated, but it exhibited an actual post-irradiation increase. This increase in post-irradiation intestinal submucosal blood flow began within 5 min after irradiation and lasted for at least 90 min. Post-irradiation haematocrits were 10.5 per cent higher than those obtained before irradiation and those obtained from sham-irradiated subjects. Histopathological examination of ileal mucosa revealed significant pathologic lesions in some irradiated animals within two hours after exposure.

Response of cerebral circulation to topical histamine.

To study the effect of histamine (HA) on brain blood flow and capillary permeability, bilateral parietal craniectomies were made in cats anesthetized with nitrous oxide and ketamine. The dura was removed and solutions of HA in mock cerebrospinal fluid (CSF) in varying concentrations ranging from 10(-5) M to 10(-1) M were irrigated continuously onto the exposed brain while local cerebral blood flow was determined polarographically by hydrogen clearance. Capillary permeability was assessed by determining HA's effect on the 125I-albumin space of the brain. Electrical activity was monitored by electrocorticography. HA consistently dilated pial blood vessels and produced within 15 min a dose-related local hyperemia that subsided 30--60 min after HA was removed. Hyperemia was blocked by cimetidine. HA had no appreciable effect on either the blood-brain barrier to albumin or the electrical activity of the cortex. HA is pharmacologically capable of participating directly in the acute hyperemic response of the brain's microcirculation to physiologic and pathologic stimuli but has little effect on cerebrovascular permeability to protein.

Experimental delayed radiation necrosis of the brain. Part 1: Effect of early dexamethasone treatment.

The authors have designed an experiment to detect a hitherto unrecognized interaction between high doses of the glucocorticoid, dexamethasone, and brain irradiation. Eighteen juvenile male rhesus monkeys received 1800 rads to the whole brain in 8.5 minutes. For 1 1/2 days before and 10 1/2 days after the irradiation, nine animals received approximately 2.9 mg/kg/day of dexamethasone intramuscularly in addition to irradiation, while the remaining nine animals served as the control group and received saline. All animals eventually developed a progressive neurological syndrome, and died of delayed radiation necrosis of the brain. The two groups were compared with regard to latency to onset of clinical signs, survival time, and number, distribution, and location of lesions of radionecrosis. Large doses of desamethasone did not alter the susceptibility of the primate brain to delayed radiation necrosis. Detailed morphological study of the radionecrotic lesions supports the hypothesis that most, if not all, of the lesions develop as the consequence of injury to blood vessels.

Cerebral blood flow in the monkey after focal cryogenic injury.

A focal cryogenic lesion was made in the left superior frontal gyrus of the anesthetized macaque brain. Cerebral blood flow (CBF) was determined by the hydrogen clearance technique before and during the 4 hours following trauma. Local CBF in tissue adjacent to the lesion increased in the first half hour after the lesion was made and then decreased during the ensuing 3 1/2 hours. Local CBF in the contralateral superior frontal gyrus, as well as total CBF and oxygen consumption, were unchanged by cryogenic trauma. The spread of vasogenic edema into uninjured tissue probably accounts for the observed decrease in local CBF. This experimental model may assist in discovering therapy to alter favorably the spatial and temporal profile of pathologic CBF changes in tissue surrounding an acute lesion of the brain.

Effect of topically applied serotonin on local cerebral blood flow.

It has been hypothesized that acute lesions of the brain enlarge through an autodestructive process. Serotonin (5HT), a potent cerebral vasoconstrictor, is believed by some to mediate the process by reducing cerebral blood flow (CBF) in tissue surrounding the lesion. The hypothesis was tested in cynomologus monkeys anesthetized with ketamine and nitrous oxide. Craniectomies, 7 mm in diameter, were performed in each parietal area. The dura was opened and polarographical electrodes of thin platinum wire were inserted into the parietal lobe cortex of each hemisphere. Mock cerebrospinal fluid (CSF) was irrigated continously onto the brain surrounding the electrodes, from which local CBF was determined repeatedly by the hydrogen-clearance technique. After baseline CBF was established, solutions of 5HT in mock CSF (in concentrations of 5 X 10(-7) M, 5 X 10(-5) M, and 5 X 10(-3) M) were irrigated onto one hemisphere while the opposite hemisphere served as control. 5HT failed to change CBF. Although 5HT is a potent vasoconstrictor, under physiologic conditions it apparently is unable to effect hemodynamically significant constriction of the peripheral cerebral vasculature of the anesthetized monkey brain.

Blood flow and oxygen consumption of the focally traumatized monkey brain.

The exposed left superior frontal gyrus of the anesthetized macaque brain was focally traumatized by a jet of compressed air. Focal blood flow in tissue around the lesion and total cerebral blood flow was determined before and during the 4 hours after trauma by the hydrogen clearance technique. Blood flow fell in tissue adjacent to the injured brain but the reduction was not statistically significant. Total cerebral blood flow, blood flow in the right superior-frontal gyrus, and oxygen consumption of the brain was unaffected by the trauma. The authors conclude that neither spreading ischemia within uninjured tissue surrounding focally traumatized brain nor posttraumatic diaschisis is readily provoked in the anesthetized brain of the monkey.

Radiation-released histamine in the rhesus monkey as modified by mast-cell depletion and antihistamine.

4000 rads of mixed gamma neutron radiation administered to rhesus monkeys released a significant amount of histamine into their circulation. When the monkeys were treated with a mast-cell histamine depleter (compound 48/80) for 4 days and then irradiated, no increase in circulating histamine was seen. When 48/80 was give 20 min after irradiation, only a slight increase in histamine was seen, indicating that 4000 rads had released most of the mast-cell histamine.

Sources of error in measuring cerebrospinal fluid formation by ventriculocisternal perfusion.

Ventriculocisternal perfusion is regarded as a precise method of measuring the rate of formation of cerebrospinal fluid (CSF) but it possesses inherent potential sources of error. Using the technique to measure CSF formation rate in the rhesus monkey, we have observed rate changes when none were expected. Most puzzling has been the steady decline of CSF formation rate at 4 percent each hour during the final five hours of a seven hour perfusion although variables known to affect CSF formation remained stable. In addition, alterations in rate caused by artefacts were observed in experiments in which craniospinal blood volume was changed by sudden changes of either PCO2 or central venous pressure. Mobilisation or sequestration of incompletely equilibrated CSF is believed responsible. In other experiments, a small increase of intracranial pressure produced by increasing outflow resistance was quickly followed by an apparent reduction of CSF formation. We have concluded that to assess accurately the effect a variable has on the rate of CSF formation, one must control perfusion time and craniospinal blood volume as well as intracranial pressure.

Histamine-induced hypotension modified by H1 and H2 antagonists in the monkey (Macaca mulatta).

Blocking H2 receptors with burimamide in the dose used (20 mg/kg) approximately doubles the amount of histamine needed to produce the same effect as seen when H1 antagonists (chlorpheniramine or mepyramine) are used alone. The Kz ratios for chlorpheniramine-chlorpheniramine plus burimamide are 117-204 and for mepyramine-mepyramine phus burimamide are 200-478. H1 and H2 receptors, in the monkey, when stimulated, both cause cardiovascular responses in the same direction.

PCO(2) and rate of formation of cerebrospinal fluid in the monkey.

Changes in cerebrospinal fluid formation rate (VF) with hypocapnia were measured by the ventriculocisternal perfusion technique in 24 rhesus monkeys anesthetized with nitrous oxide. In addition cerebral blood flow (CBF) was measured by the hydrogen clearence methods, Vf in control animals declined at a mean rate of 2.3 mul/min each hour during the last 4.5 h of a 7-h perfusion although variables known to effect Vf remained stable. Three hours after perfusion began, Vf of normocapnic controls was 41.4 mul/min +/- 5.4; CBF, 59P ML/100 G PER MIN. When Pco(2) was reduced to half of control, Vf fell to 35.6 mul/min +/- 6.3 and CBF fell by 27%. When Pco(2) was doubled, Vf fell to 33.1 mul/min +/- 5.3 and CBF increased threefold. The difference in Vf id significant only for the hypercapnic group (p=0.01). When animals were used as their own controls, three were no significant differences in Vf with hypercapnia compared to normocapnia. These results indicated that in the monkey variations of Pco(2) within broad physiologic limits, which are sufficient to cause large changes in CBF, have little effect of Vf.

The effect of antihistamines on experimental posttraumatic edema of the spinal cord.

The present experiments were designed to test the effect of antihistamines on the formation of post-traumatic edema of the spinal cord. Ten rhesus monkeys received 600 gm cm injuries to the T10 level of the spinal cord. Five animals received antihistamine treatment and five animals acted as untreated controls. Posttraumatic edema was estimated using radio-active tagged serum albumin. A significant increase in radioactivity of the injured segment was demonstrated in both groups when compared to noninjured issue, but no difference was demonstrated in the radioactivity of the injured segment in the treated versus the nontreated group.