The rate of intravenous cocaine administration alters c-fos mRNA expression and the temporal dynamics of dopamine, but not glutamate, overflow in the striatum.

The rapid entry of drugs into the brain is thought to increase the propensity for addiction. The mechanisms that underlie this effect are not known, but variation in the rate of intravenous cocaine delivery does influence its ability to induce immediate early gene expression (IEG) in the striatum, and to produce psychomotor sensitization. Both IEG induction and psychomotor sensitization are dependent upon dopamine and glutamate neurotransmission within the striatum. We hypothesized, therefore, that varying the rate of intravenous cocaine delivery might influence dopamine and/or glutamate overflow in the striatum. To test this we used microdialysis coupled to on-line capillary electrophoresis and laser-induced fluorescence, which allows for very rapid sampling, to compare the effects of a rapid (5 s) versus a slow (100 s) intravenous cocaine infusion on extracellular dopamine and glutamate levels in the striatum of freely moving rats. An acute injection of cocaine had no effect on extracellular glutamate, at either rate tested. In contrast, although peak levels of dopamine were unaffected by infusion rate, dopamine levels increased more rapidly when cocaine was administered over 5 versus 100 s. Moreover, c-fos mRNA expression in the region of the striatum sampled was greater when cocaine was administered rapidly than when given slowly. These data suggest that small differences in the temporal dynamics of dopamine neurotransmission may have a large effect on the subsequent induction of intracellular signalling cascades that lead to immediate early gene expression, and in this way influence the ability of cocaine to produce long-lasting changes in brain and behavior.

Requirement of endogenous basic fibroblast growth factor for sensitization to amphetamine.

Repeated exposure to amphetamine produces long-lasting increases in sensitivity to its effects. We reported previously that repeated amphetamine treatment results in increased astrocytic expression of basic fibroblast growth factor (bFGF) in the ventral tegmental area (VTA) and substantia nigra compacta (SNc) and that this effect is prevented by coadministration of a nonspecific glutamate receptor antagonist. Here we show that the development of sensitization to amphetamine is prevented when amphetamine injections are preceded by infusions of a neutralizing antibody to bFGF into the VTA. In addition, we show that astrocytic bFGF expression is increased in the VTA and SNc of animals that exhibit behavioral sensitization and that the number of bFGF-immunoreactive astrocytes in these regions is strongly and positively correlated with the magnitude of sensitization. Cotreatment with an NMDA glutamate receptor antagonist blocks both the development of behavioral sensitization and bFGF induction. These results show that endogenous bFGF is necessary for the development of sensitization to amphetamine and suggest that bFGF mediates the glutamatergic-dopaminergic interaction that initiates the long-term consequences of repeated drug use.

The development of olfactory conditioned ejaculatory preferences in the male rat. II. Parametric manipulation of conditioning session number and duration.

We have previously demonstrated that repeated pairing of a neutral odor with copulation produces a subsequent conditioned ejaculatory preference (CEP) for females bearing that odor. The present study examines the course of CEP development. In Experiment 1, Long-Evans male rats were allowed access to almond-scented, sexually receptive females for either one, five, or nine conditioning sessions that were 30 min in duration. Males given five or nine sessions displayed significant CEPs. In Experiment 2, male rats were given a single conditioning session with multiple almond-scented females until either a duration (60, 120, 180, or 240 min) or copulatory criterion (two, four, or six ejaculatory series) was satisfied. Males that received 120-, 180-, or 240-min sessions or four ejaculations displayed significant CEPs; males that received two or six ejaculations displayed a trend for CEPs. Analysis of effect size estimates revealed that the strongest CEPs were produced by 120 min of copulation or four ejaculations. In Experiment 3, males receiving nine conditioning sessions each 30 min in duration displayed a more enduring CEP than did males receiving a single conditioning session 240 min in duration. These data suggest that early sexual experiences have particularly powerful influences on subsequent sexual preferences and that the development of sexual preferences are influenced by interactions between CS-UCS pairings and motivational variables.

Post immunization Hib antigen detection in the CSF of a patient with meningococcal meningitis.

We report a case of meningococcal meningitis where the cerebrospinal fluid was negative for Neisseria meningitidis but positive for Haemophilus influenzae type b by rapid antigen detection test. We believe that this was due to prior immunization with Haemophilus influenzae type b vaccine. We recommend caution in interpretation of the rapid antigen detection tests especially in patients who had been vaccinated against organisms screened by these tests.

Corneal microsporidiosis. Report of case, including electron microscopic observations.

OBJECTIVE: To report a case of corneal stromal infection caused by a protozoon of the genus MICROSPORIDIA:, including clinical, histopathologic, and electron microscopic observations. DESIGN: Case report. METHODS: Light and electron microscopy studies were performed on keratectomy specimens from a 67-year-old immunocompetent man who had a unilateral chronic stromal keratitis that was refractory to medical treatment. Initial corneal biopsy followed by lamellar and penetrating keratoplasty were performed on the patient. All the specimens were studied histopathologically. RESULTS: Light microscopy of the corneal biopsy and the subsequent keratectomy specimens demonstrated myriad small, round to oval microsporidial organisms measuring 3.5 to 5.0 micrometer in length that stained positively with the periodic acid-Schiff, Grocott-methenamine silver, and acid-fast methods and were gram positive. Electron microscopic observations demonstrated viable blastospores that had a thin osmiophilic outer cell wall and contained 11 to 13 coils of the filament. The light and electron microscopic features, the tinctorial characteristics, and the selective corneal stromal involvement are consistent with microsporidial keratitis. CONCLUSIONS: Microsporidiosis should be considered in the differential diagnosis of a culture-negative stromal keratitis refractory to medical treatment. The diagnosis can be easily established based on the morphologic features of the protozoa in the keratectomy specimens. No effective medical treatment for the stromal disease is available. Full-thickness keratoplasty is suggested because, in our patient, lamellar keratoplasty did not preclude recurrence of the disease.