Larry A. Grupp

A naturalistic visual scanning approach to assess selective attention in major depressive disorder

Cognitive biases in information processing play an important role in the etiology and maintenance of emotional disorders. A new methodology to measure attentional biases is presented; this approach encourages subjects to scan and re-scan images with different thematic content, while the pattern of their attentional deployment is continuously monitored by an eye-tracking system. Measures of attentional bias are the total fixation time and the average glance duration on images belonging to a particular theme. Results showed that subjects with depressive disorder (n=8; Beck Depression Inventory Score>/=16) spent significantly more time looking at images with dysphoric themes than subjects in the control group (n=9). Correlation analysis revealed that the differences between the fixation times of the two groups are significantly correlated with the valence ratings, but not with the arousal ratings of the images. The average glance duration on images with social, neutral and threatening themes were similar for both groups, while the average glance duration on images with dysphoric themes was significantly larger for subjects with depressive disorder. The above results suggest that subjects with depressive disorder selectively attend to mood-congruent material and that depression appears to influence the elaborative stages of processing when dysphoric images are viewed.

Calculated bioavailable testosterone levels and depression in middle-aged men

BACKGROUND The association between circulating total testosterone (TT) levels and depressive symptoms remains unclear. We sought to determine the relationship between physiologically active bioavailable testosterone (BT) and depressive symptoms in middle-aged men with and without major depressive disorder (MDD). METHODS We assessed and compared calculated BT levels in two groups of middle-aged men (40-65 years): untreated subjects meeting DSM-IV-TR-defined criteria for a major depressive episode as part of major depressive disorder (N=44) and a matched non-depressed control group (N=50). RESULTS Depressed men had lower mean BT levels (3.51+/-1.69 vs. 4.69+/-2.04 nmol/L; p=0.008) and TT levels (11.94+/-4.63 vs. 17.64+/-1.02 nmol/L; p<0.001) when compared to the control group. Biochemical hypogonadism (i.e., BT level< or =2.4 nmol/L or TT level< or =12.14 nmol/L) was also more prevalent in depressed men vs. non-depressed controls (34% vs. 6%, p<0.001; 61% vs. 14%, p<0.001, respectively). CONCLUSIONS Changes in physiologically active BT concentration may be a vulnerability factor for depressive symptoms in middle-aged depressed men.

Angiotensin II reduces voluntary alcohol intake in the rat

The voluntary intake of alcohol has been shown to be attenuated by a variety of manipulations which increase activity in the renin-angiotensin system. In the present study we examined the effects of peripheral injections of the peptide angiotensin II on alcohol drinking. The peptide produced a dose-dependent decrease in alcohol intake with 20 micrograms/kg having little effect, 200 micrograms/kg reducing intake by approximately 50% and 1 mg/kg virtually abolishing all alcohol drinking. This decrease was not due to a peptide induced motor deficit, or state of sickness, and could also not be accounted for by the increased water intake, or by a change in pharmacokinetics and taste function. These data provide direct evidence that angiotensin II can modulate voluntary alcohol drinking. The possibility that the level of angiotensin II serves as a satiety signal in alcohol drinking is discussed.

Biphasic action of ethanol on single units of the dorsal hippocampus and the relationship to the cortical EEG

The effects of four doses of ethanol (100, 200, 400, 800 mg/kg) administered IV, on the spontaneous firing rate of single units in the dorsal hippocampal region of the rat were studied. At the lower doses, a mixture of excitatory and inhibitory effects occurring in that order was seen, reflecting a biphasic action of ethanol at the level of the single neuron. As the dose increased, the excitation disappeared and successively greater degrees of response inhibition prevailed. The pattern of the fronto-cortical EEG changed from predominantly low amplitude fast activity with a few episodes of high amplitude slow activity at low doses, to more sustained episodes of slow activity at high doses. The time-response curve showed that the peak of maximum inhibition seen at the highest dose occurred with a longer latency than the peak of maximum excitation seen at the lower doses. Finally, the changes in unit firing appeared to follow four general patterns and to be correlated with the mode of fronto-cortical EEG activity.

Effects of pimozide on the acquisition, maintenance, and extinction of an amphetamine-induced taste aversion

Different groups of rats were pretreated with the dopamine receptor blocker, pimozide (0.25, 0.5, or 1.0 mg/kg), in an attempt to investigate the role of dopaminergic transmission in the acquisition, maintenance, and extinction of a taste aversion produced by d-amphetamine sulphate (1.0 or 2.0 mg/kg). In the first phase of the experiment, all doses of pimozide attenuated but did not block the acquisition of the aversion produced by 1.0 mg/kg but not by 2.0 mg/kg amphetamine. In Phase II, pimozide pretreatment was suspended to allow the attenuated groups to acquire the aversion and then reintroduced in Phase III. In this phase all groups continued to avoid the taste, indicating a failure of pimozide to affect the maintenance of the avoidance response. When amphetamine treatment was suspended in Phase IV, pimozide accelerated the extinction, especially in those groups that had previously received the 1.0 mg/kg dose of amphetamine. These results are discussed with reference to dopaminergic mechanisms in avoidance learning and a pimozide-mediated reduction in functional strength of amphetamine as an unconditioned stimulus.

An investigation of the interaction between the reinforcing properties of food and ethanol using the place preference paradigm

Abstract 1. 1. For three groups of rats, intraperitoneal injections of either 250, 500, or 1000 mg/kg ethanol were paired with a distinctive environment and later a choice was offered between that environment and one that had previously been associated with saline injections. 2. 2. For a second set of three groups of animals the identical procedure was followed except that food was available in both the environment paired with ethanol and the one paired with saline. 3. 3. The rats showed no preference or aversion for the environment paired with the 250 mg/kg dose either when the drug was given alone or when combined with the availability of food. No preference or aversion for the 500 mg/kg dose was indicated when the drug was given alone, but the same dose combined with food was preferred to food plus saline. The 1000 mg/kg dose was found to be aversive when given by itself, yet the same dose was neither aversive nor preferred when combined with the availability of food. 4. 4. These findings suggest that ethanol can interact with food, a positive reinforcer, in ways that cannot be predicted from the effect of the drug when presented alone.

Conditioned place aversion mediated by self-administered ethanol in the rat: a consideration of blood ethanol levels

A previous experiment has shown that rats will avoid environmental cues that have been associated with a history of ethanol self-administration. One possible explanation for this conditioned place aversion may be related to the temporal parameters of that experiment. During the initial segment of each 90-min conditioning/drinking trial (when most of the drinking occurred) the blood ethanol levels (BELs) were low and may well have produced positive effects at that time. However, as the drug continued to be absorbed and BELs increased during the remainder of the 90-min trial, the final (and conditioned) drug effects may have been aversive. In the present experiment the trial length was shortened to a 15-min period so that only low BELs would be temporally paired with the conditioning environment. A conditioned preference for that environment was predicted. Twelve rats were trained to self-administer ethanol in one environment and had water available in a different environment. Eight control animals had only water in both environments. BELs were measured and found to be low (16.8 to 57.6 mg%) and rising during the conditioning trials. However, when given a choice between the two environments, the rats avoided the environment in which they formerly consumed ethanol. No change in preference was noted for the control animals. This result was in accordance with previous findings but did not support the hypothesis that low, excitatory BELs would mediate a conditioned place preference in the rat.

Some determinants of the motivational properties of ethanol in the rat: Concurrent administration of food or social stimuli

The hypothesis was examined that the interaction of ethanol with the conditions under which it is administered may determine whether either preference or aversion for the drug develops. In Experiment 1, eight groups of food-deprived rats received injections of ethanol (175–1,400 mg/kg) in one environment and were later offered a choice between that environment and a different one previously associated with saline injections. Another eight groups were treated identically, except that food was available in both the saline and ethanol-paired environments. The groups given the drug without food showed no preference or aversion at low doses (175–700 mg/kg), but showed aversion at higher doses (1,000 and 1,400 mg/kg). When food was available, there was an increased preference for the environment paired with the 500 mg/kg doses. In Experiment 2, placing two rats together increased each rats preference for the environment associated with the other animal. However, rats pretreated with 500 mg/kg ethanol before being placed together showed a reduced preference for the environment associated with the drug and the other animal. Controls never paired with another rat showed no preference or aversion at the same ethanol dose. Thus, ethanol may interact with conditions such as the presence of food or another animal to determine final effects that are unique to those conditions.

Regulation of alcohol consumption by the renin-angiotensin system: a review of recent findings and a possible mechanism of action.

The renin-angiotensin system has traditionally been associated with the regulation of fluid and electrolyte balance. In this review we summarize the data which ascribes a completely new function to this system, i.e., the regulation of alcohol consumption. In addition, we suggest a possible mechanism for this effect based on the concept of a satiety or stop process. The approach taken was to examine the effect on alcohol intake of a wide variety of drug, genetic, dietary, surgical and neurosurgical manipulations, each of which has a range of biological effects characteristic of that manipulation, but all of which share the common property of altering activity in the renin-angiotensin system. The effect of these manipulations on alcohol intake was most parsimoniously explained by reference to their ability to raise or lower activity in the renin-angiotensin system. Any intervention which modulates activity in this system, either directly or indirectly, is likely to have consequences for alcohol consumption.

Voluntary alcohol intake in the hypertension prone Dahl rat

Previous work in our laboratory has shown that alterations in the sodium content of the diet which alter salt appetite, can modify ethanol self-selection and intoxication. The present experiment investigates the relationship between the intakes of sodium and ethanol on the one hand and the development of hypertension, by measuring voluntary ethanol consumption and blood pressure in two rat lines, the salt sensitive (SS) and salt resistant (SR) Dahl rats, specially bred to show differential sensitivity to dietary sodium supplements. All rats were given 24 hr access to 6% (v/v) ethanol and water and first offered a control diet (0.5% Na) followed by a 4% and then an 8% sodium supplemented diet. While on the control diet there were significant between strain differences in ethanol consumption, suggesting that the SS animals came genetically prepared to consume more ethanol. Blood pressure measured at regular intervals indicated significant changes only in the SS rats even though both lines as well as a group of Wistar rats, added for purposes of comparison, all increased their ethanol intake to the salt supplemented diets. A second experiment suggested that the initial difference in consumption between the SS and SR lines may be related to central nervous system sensitivity since differences were found in salt appetite but not in taste sensitivity or in the absorption, distribution or metabolism of the drug. These findings demonstrate that the Dahl SS rat is predisposed to consume more ethanol than the SR rat even before exposure to the hypertension-inducing diet, and that this predisposition is probably central in origin.(ABSTRACT TRUNCATED AT 250 WORDS)