Effects of temperature on cuticular lipids and water balance in a desert Drosophila: is thermal acclimation beneficial?

The desert fruit fly Drosophila mojavensis experiences environmental conditions of high temperature and low humidity. To understand the physiological mechanisms allowing these small insects to survive in such stressful conditions, we studied the effects of thermal acclimation on cuticular lipids and rates of water loss of adult D. mojavensis. Mean hydrocarbon chain length increased at higher temperatures, but cuticular lipid melting temperature (Tm) did not. Lipid quantity doubled in the first 14 days of adult life, but was unaffected by acclimation temperature. Despite these changes in cuticular properties, organismal rates of water loss were unaffected by either acclimation temperature or age. Owing to the smaller body size of warm-acclimated flies, D. mojavensis reared for 14 days at 33 degrees C lost water more rapidly on a mass-specific basis than flies acclimated to 25 degrees C or 17 degrees C. Thus, apparently adaptive changes in cuticular lipids do not necessarily result in reduced rates of water loss. Avoidance of high temperatures and desiccating conditions is more likely to contribute to survival in nature than changes in water balance mediated by surface lipids.

Use of low-dose fluoxetine in major depression and panic disorder.

BACKGROUND: Recent reports suggest that fluoxetine in doses less than the standard 20 mg/day may be effective in the treatment of depression and that some patients, particularly those with panic disorder, may be intolerant of the 20 mg/day dose. We examined the utility of starting fluoxetine at a low daily dose (5 mg) and increasing to the standard daily dose (20 mg) in depressed outpatients with and without concurrent panic disorder. METHOD: One hundred thirty-three consecutive outpatients meeting DSM-III-R criteria for major depression were studied. Patients were started on fluoxetine 5 mg/day and were gradually increased to 20 mg/day over a 1-week period. Patients who were unable to reach the 20 mg/day dose were instructed to take the highest tolerable dose for the duration of the study. After a month of fluoxetine treatment, patients were evaluated for compliance with treatment and improvement on the Clinical Global Improvement scale. RESULTS: Twenty-eight percent of the patients were unable to increase the dose to the full 20 mg. Of these patients, half could not tolerate doses lower than 20 mg and discontinued the drug, while the other half did well clinically on the lower doses. Patients who discontinued fluoxetine tended to have panic disorder in addition to depression. CONCLUSION: We conclude that starting fluoxetine at doses lower than 20 mg is a useful strategy because of the substantial fraction of patients who cannot tolerate a 20-mg dose but appear to benefit from lower doses. This dosing strategy may be of particular benefit for patients with panic disorder.

Systemic hypertension associated with tricyclic antidepressant treatment in patients with panic disorder.

In a sample of 114 patients, 6 patients developed hypertension while taking tricyclic antidepressants. All these patients were diagnosed as having panic disorder, with or without major depression. Half of the 6 patients had a previous diagnosis of hypertension, which had been well controlled by antihypertensive drugs for years. A comparison group of patients with major depression, who had never had panic attacks, had no cases of hypertension induced by these antidepressants. These findings raise the possibility that patients who have panic disorder may experience cardiovascular disregulation that increases their risk for antidepressant-induced hypertension.

Attenuation of opioid receptor activity by phorbol esters in neuroblastoma x glioma NG108-15 hybrid cells.

Chronic opioid treatment of neuroblastoma x glioma NG108-15 cells induces desensitization of the opioid receptor and this may involve a change in membrane protein phosphorylation. In an attempt to mimic this possible mechanism, we studied effects of phorbol ester activation of protein kinase C on opioid receptor activity. Incubation of NG108-15 hybrid cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) abolished up to 45% of opioid inhibition of cyclic AMP accumulation in intact cells, while basal accumulation and prostaglandin E1-stimulated cyclic AMP accumulation were unaltered. This decrease of opioid inhibition was dose- and time-dependent and the potency order of phorbol esters and apparent K activation (90 nM) for TPA were consistent with phorbol esters acting through the stimulation of protein kinase C. TPA also decreased the inhibition of cyclic AMP accumulation mediated through muscarinic and alpha-2 adrenergic receptors. These effects of TPA were best explained by a TPA-induced alteration of the inhibitory nucleotide-binding protein (Gi), the common transducer protein of these receptors. Impairment of Gi by TPA treatment was evidenced by a reduction in agonist-stimulated GTP hydrolysis and activation by GTP. Quantification of Gi by pertussis toxin-catalyzed ADP-ribosylation revealed that TPA decreased maximal labeling. In summary, phorbol esters appeared to attenuate opioid receptor activity by altering the activity of the transducer protein Gi.

Treatment of cocaine-induced panic disorder.

The authors describe 10 patients who developed panic attacks only after substantial cocaine use. The timing of the onset of symptoms, i.e., after 1-6 years of cocaine use, and the fact that only one patient had a first-degree relative with panic disorder were more suggestive of acquired than primary panic disorder. The patients' atypical symptoms and responses to medications may be explained in terms of limbic-neuronal hyperexcitability induced by cocaine through a kindling mechanism.

Modification of opioid receptor activity by acid phosphatase in neuroblastoma x glioma NG108-15 hybrid cells.

Opioid receptor activity in neuroblastoma x glioma NG108-15 hybrid cell membranes was attenuated by acid phosphatase purified by high performance liquid chromatography and devoid of protease activity. Treatment of membranes with this phosphatase decreased opioid inhibition of adenylate cyclase and this effect was potentiated by the presence of the opioid agonist during the phosphatase treatment. Phosphatase treatment did not affect the number of opioid receptors but it did alter the distribution of receptors among affinity states, by increasing the percentage of receptors in the low affinity state. The similarities between these effects and desensitization of the opioid receptor, during chronic opioid treatment, are discussed.

Cell-free desensitization of opioid inhibition of adenylate cyclase in neuroblastoma X glioma NG108-15 hybrid cell membranes.

When membranes from neuroblastoma X glioma NG108-15 hybrid cells were incubated in a cell-free system with opioid agonists, a time-, temperature-, and dose-dependent desensitization to opioid inhibition of adenylate cyclase activity was observed. The composition of the system during the incubation was manipulated to elucidate the biochemical mechanisms of desensitization. Receptor coupling appeared to be a prerequisite for desensitization, because both magnesium and sodium, which are necessary for coupling, were required for desensitization. Removal of ATP and addition of cyclic AMP or cyclic GMP had no effect on desensitization.

Effect of pertussis toxin treatment on the down-regulation of opiate receptors in neuroblastoma X glioma NG108-15 hybrid cells.

Chronic treatment of neuroblastoma X glioma NG108-15 hybrid cells with 10 nM [D-Ala2,D-Leu5] enkephalin (DADLE) results in a reduction of cell-surface opiate delta receptors. Whether opiate receptor internalization requires the activation of the guanine nucleotide-binding protein (Ni) is unclear. Hence, activation of Ni was attenuated by treating hybrid cells with 100 ng/ml pertussis toxin (PT) for 3 h, which resulted in a decrease in DADLE's ability to inhibit adenylate cyclase activity. Despite this prior treatment with PT, chronic exposure of these cells to 10 nM DADLE resulted in a time-dependent decrease in both [3H]diprenorphine and [3H]DADLE binding. This reduction in 3H-ligand binding in cells previously treated with PT represented internalization of the receptors because translocation was observed of bound [3H]DADLE from plasma membrane fractions to the lysosomal fractions in the Percoll gradients. Thus, opiate receptors internalize without activation of Ni. The internalization of opiate receptors was not accompanied by Ni. By measuring the amount of the 41-kDa alpha subunit being labeled by PT with [32P]NAD+, it was determined that plasma membrane preparations, of both the control cells and cells treated with 10 nM of DADLE for 4 h, contained equal concentrations of Ni, 2 pmol of Ni/mg of protein. Additionally, there was no measurable alteration in the amount of PT substrate in the lysosomal fractions of the DADLE-treated cells as compared to that of control cells. Chronic DADLE treatment resulted in a decrease in Km value of NAD+ in the ADP-ribosylation of 41-kDa subunit of Ni. In summary, opiate receptors internalize as agonist-receptor complexes without the guanine nucleotide-binding component.

Lithium potentiation of antidepressant treatment.

The addition of lithium carbonate to an antidepressant drug regimen in depressed patients initially unresponsive to the antidepressants alone has been reported to bring about rapid improvement in the majority of these individuals. Nine additional cases are reported in this article. The response to lithium addition was more variable than described previously. Two patients showed sustained improvement, two showed transient improvement but then relapsed, two other cases with bipolar histories became manic, and three did not respond at all. Possible reasons for this variability are discussed.

The treatment requests of alcoholics.

Two hundred and thirty-four alcoholic patients at a general hospital outpatient clinic were administered a questionnaire to ascertain their treatment requests. One year later information characterizing the patients and their treatment outcomes was obtained by chart review and therapists' ratings. The alcoholics' treatment requests were similar to those obtained previously with general psychiatric populations. The most frequent requests were for psychological treatments: 'clarification of issues' or 'psychodynamic insight' while requests for administrative help or social intervention were least frequent. Requesting psychological treatments did not significantly predict engaging in psychotherapy or change during therapy. Requesting help with the complications of drinking only and not psychological help predicted early drop out. Medical, administrative and social intervention requests predicted poor improvement in drinking behavior during therapy.

Effects of d-amphetamine and pentobarbital under concurrent fixed-ratio schedules.

Pigeons were studied under a two-key concurrent fixed-ratio schedule of food presentation. During the first five sessions, the fixed-ratio requirements were 30 responses on one key (major key) and 120 responses on the other key (minor key): responding occurred almost exclusively on the major key. When the fixed-ratio requirements were then made equal at 30 responses on both keys, responding continued to predominate on the major key. The asymmetric distribution of responses persisted when the concurrent fixed-ratio fixed-ratio schedule was interrupted with periods during which the major key was associated with extinction while the other key remained associated with a fixed-ratio schedule. Additionally, in some subjects the fixed-ratio requirements were increased. These schedule modifications decreased the asymmetry in responding but did not eliminate it. d-Amphetamine decreased rates on both keys and slightly increased the asymmetric distribution of responses, while pentobarbital reversed the distribution of responses by increasing low rates and decreasing high rates. The pigeons maintained their original asymmetric distribution of responses during the 1 1/2-year-long study, despite schedule alterations and drug administrations.