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RATIONALE: The abuse of the psychostimulant methamphetamine (MA) is associated with substantial costs and limited treatment options. To understand the mechanisms that lead to abuse, animal models of voluntary drug intake are crucial. OBJECTIVES: We aimed to develop a protocol to study long-term non-invasive voluntary intake of MA in mice. METHODS: Mice were maintained in their home cages and allowed daily 1 h access to an attached tunnel leading to a test chamber in which nebulized MA was available. Restated, if they went to the nebulizing chamber, they self-administered MA by inhalation. This protocol was compared to injected and to imposed exposure to nebulized MA, in a series of seven experiments. RESULTS: We established a concentration of nebulized MA at which motor activity increases following voluntary intake resembled that following MA injection and imposed inhalation. We found that mice regulated their exposure to MA, self-administering for shorter durations when concentrations of nebulized MA were increased. Mice acquire the available MA by repeatedly running in and out of the nebulizing chamber for brief bouts of intake. Such exposure to nebulized MA elevated plasma MA levels. There was limited evidence of sensitization of locomotor activity. Finally, blocking access to the wheel did not affect time spent in the nebulizing chamber. CONCLUSIONS: We conclude that administration of MA by nebulization is an effective route of self-administration, and our new protocol represents a promising tool for examining the transitions from first intake to long-term use and its behavioral and neural consequences in a non-invasive protocol.

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Copulation induces hypothalamic release of neuropeptides and catecholamines, especially gonadotropin-releasing hormone (GnRH) and norepinephrine, in female rabbits. The forebrain distribution of GnRH cells and the cellular events responsible for the coitally induced GnRH surge have not been identified. We characterized the expression of c-fos mRNA before (0 min) and up to 60 min after coitus in forebrain tissues of mated and nonmated females and compared these findings with those in which single- and double-labeled GnRH/Fos protein cells were identified by immunocytochemistry (ICC). Enhanced expression of fos-mRNA occurred 30 min after coitus, especially in the anteroventral periventricular nucleus (AVPV), the encapsulated portion of the bed nucleus of the stria terminalis (BNSTe) and the ventrolateral hypothalamus (VLH); this increased fos-mRNA activity remained elevated at 60 min in the AVPV and VLH, and was reflected by Fos protein expression 90 min postcoitus. Both ICC Fos-labeled and ICC GnRH-labeled cells were widely distributed throughout the forebrain with postcoital increased double-labeling in the preoptic-septal areas, the anterior-medial hypothalamus and the VLH. The increased number of dual-labeled and unchanged number of single-labeled GnRH cells after coitus suggest some GnRH neurons were non-detected before coitus. Many dual-labeled neurons were adjacent to Fos-labeled cells, suggesting enhanced interneuronal input to GnRH cells after coitus. Collectively, the results suggest that coitus activates hypothalamic GnRH neurons via several loci that include the AVPV, BNSTe and VLH. The distinct anatomical location of the AVPV, BNSTe and VLH further suggests that coital signals may reach the hypothalamus via separate neural pathways that are likely developed within the brainstem.

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PURPOSE: Patient-centered interviewing is associated with greater patient satisfaction and better medical outcomes than traditional encounters, but actively seeking patients' views of their illnesses and encouraging patients to express expectations, thoughts, and feelings is difficult in encounters that require an interpreter. We sought to examine physicians' use of the patient-centered approach with patients who required the assistance of an interpreter. SUBJECTS AND METHODS: A cross-sectional sample of patients was videorecorded during visits with physicians at a multi-ethnic, university-affiliated, primary care clinic. Nineteen medical encounters of Spanish-speaking patients who required an interpreter and 19 matched English-speaking encounters were coded for frequency that patients mentioned symptoms, feelings, expectations, and thoughts (collectively called "offers"). Physicians' responses were coded as ignoring, closed, open, or facilitative of further discussion. RESULTS: English-speaking patients made a mean (+/- SD) of 20 +/- 11 offers, compared with 7 +/- 4 for Spanish-speaking patients (P = 0.001). Spanish-speaking patients also were less likely to receive facilitation from their physicians and were more likely to have their comments ignored (P <0.005). English-speaking patients usually received an answer or acknowledgment to their questions even if the physicians did not encourage further discussion on the topic. CONCLUSION: Spanish-speaking patients are at a double disadvantage in encounters with English-speaking physicians: these patients make fewer comments, and the ones they do make are more likely to be ignored. The communication difficulties may result in lower adherence rates and poorer medical outcomes among Spanish-speaking patients.

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