Effect of muscimol on haloperidol-induced alteration of neurotensin gene expression in the striatum and nucleus accumbens in the rat.

Acute neuroleptic administration increases the expression of neurotensin/neuromedin (NT/N) gene in rat dorsolateral striatum and shell sector of the nucleus accumbens. The purpose of this study was to examine modulation of neuroleptic induction of NT/N and the proto-oncogene c-fos expression by the GABAA agonist muscimol. Adult male Sprague-Dawley rats were treated with saline, haloperidol (1 mg/kg); muscimol (3.2 mg/kg); or haloperidol (1 mg/kg) plus muscimol (3.2 mg/kg). Animals were sacrificed 1 h after drug administration. Expression of NT/N and c-fos mRNA was examined by in situ hybridization using 35S-antisense probes. Muscimol alone had no measurable effect on basal levels of NT/N or c-fos mRNA in either the dorsolateral striatum or the nucleus accumbens. However, co-administration of muscimol with haloperidol reduced haloperidol-induced increases in NT/N as well as c-fos mRNA in the dorsolateral striatum. In contrast, NT/N mRNA expression in accumbal shell induced by haloperidol was not modulated by co-administration of muscimol. These data suggest that GABAA receptors may be involved in regulation of NT/N gene expression in the DLSt, but not in the nucleus accumbens.

Differential diagnosis and psychopharmacology of dual disorders.

There are multiple potential interactions of substances of abuse with psychiatric illnesses. The individual agents, the stage of abuse, withdrawal, or recovery, and the patient's psychiatric illness must be considered as an integrated whole to ascertain the appropriate interventions. Polysubstance abuse can cause still more complicated interactions. Assessment of differential treatment needs for both the psychiatric illness component and the substance use disorder component permits both elements to be approached, often simultaneously, and can facilitate treatment of both. Ignoring either component can lead to inappropriate treatment or exacerbation of illness. The high rate of comorbidity of chemical dependence and other psychiatric illnesses is intriguing in light of studies that demonstrate vulnerability to drug abuse associated with specific alleles of the dopamine D2 receptor gene in some families. It is hoped that further investigations will shed light on the complex interactions and associations between chemical dependency and other psychiatric illnesses and result in new treatment strategies for both. In the past, many substance abuse treatment programs used to emphasize the complete cessation of all medications including some potentially beneficial prescription medications. This was likely because of previous excessive prescription by physicians of sedatives or benzodiazepines. Increasingly, recovery programs support intelligent, responsible use of nonaddictive psychiatric medications, and AA World Services prints a pamphlet supporting such physician-supervised use. Conversely, psychiatrists previously frequently overlooked or neglected diagnosis and treatment of chemical-dependency disorders. Greater efforts are needed to focus equal energy on diagnosis and treatment of chemical-dependency disorders in "psychiatric" populations. Many studies show that physicians neglect to collect adequate information and are not sufficiently aggressive in referring patients to chemical dependence treatment programs. By combining knowledge and appropriate therapeutic interventions from both psychiatric and addiction treatment fields, the needs of the dually diagnosed patient can be met more adequately.

Sporadic Creutzfeldt-Jakob disease in two coworkers.

We report the coincidence of pathologically confirmed sporadic CJD in two unrelated schoolteachers who shared a school wing for 9 months. The first developed ataxia, tremulousness, and dementia 5 months after his last contact with his colleague. Diagnosis of CJD was made 2 months later by brain biopsy. Eight months later, the second teacher developed similar symptoms and died after 9 months. Whether this unique coincidence reflects mere chance or some form of direct viral transmission is unknown. Continued epidemiologic surveillance for any future "coincidence" is warranted.

In vitro membrane association of the F0 polypeptides of the Escherichia coli proton translocating ATPase.

The F0 polypeptides a, b, and c of the H+-translocating ATPase associated with membranes when synthesized in vitro. This association occurred when the membranes were present either cotranslationally or post-translationally. In addition, the F0 polypeptides associated with liposomes. The membrane association seemed to be an insertion process since there was protection of polypeptides a and c from proteolysis. The in vitro insertion of the F0 polypeptides a, b, and c was independent of the synthesis of each polypeptide and of the F1 polypeptides.

In vitro synthesis of the F0 and F1 components of the proton translocating ATPase of Escherichia coli.

Specialized lambda transducing phage DNA containing the unc region of the Escherichia coli chromosome was used as template to direct an in vitro transcription/translation system. The results demonstrated synthesis of seven of the eight polypeptides of the proton translocating ATPase of this organism. The three polypeptides a, b, and c, constituting the F0 portion of the complex, were resolved by sodium dodecyl sulfatepolyacrylamide gel analysis and have apparent molecular weights (Mr = 24,000, 18,000, and 8,000-9,000) similar to the corresponding proteins produced in vivo. In addition, the alpha, beta, delta, and epsilon polypeptides of the F1 portion of the ATPase were also detected and their molecular weights correspond to the in vivo peptides. A 4.3-kilobase HindIII-generated lambda unc DNA fragment was cloned onto plasmid vectors and was demonstrated to contain the genes for the three F0 and two of the F1 (alpha, delta) subunits. In addition, the polypeptides synthesized in vitro were precipitable with antibody prepared against purified F1.