A complex program of striatal gene expression induced by dopaminergic stimulation.

Dopamine acting in the striatum is necessary for normal movement and motivation. Drugs that change striatal dopamine neurotransmission can have long-term effects on striatal physiology and behavior; these effects are thought to involve alterations in gene expression. Using the 6-hydroxydopamine lesion model of Parkinson's disease and differential display PCR, we have identified a set of more than 30 genes whose expression rapidly increases in response to stimulation of striatal dopamine D1 receptors. The induced mRNAs include both novel and previously described genes, with diverse time courses of expression. Some genes are expressed at near-maximal levels within 30 min, whereas others show no substantial induction until 2 hr or more after stimulation. Some of the induced genes, such as CREM, CHOP, and MAP kinase phosphatase-1, may be components of a homeostatic response to excessive stimulation. Others may be part of a genetic program involved in cellular and synaptic plasticity. A very similar set of genes is induced in unlesioned animals by administration of the psychostimulant cocaine or the antipsychotic eticlopride, although in distinct striatal cell populations. In contrast to some previously described early genes, most of the novel genes are not induced in cortex by apomorphine, indicating specificity of induction. Thus we have identified novel components of a complex, coordinated genetic program that is induced in striatal cells in response to various dopaminergic manipulations.

Psychoanalysis and its neighboring sciences: paradigms and opportunities.

Breuer and Freud's prepsychoanalytic cathartic treatment proved to be generally ineffective. Consequently, both the treatment and the theory adduced to support it were revised to accommodate the issue of wishes and their expression. But the new treatment, too, had only limited success, which resulted in a further revision of the supporting theory to emphasize the "resistances," or the control and modulation of drives. There is an irony in these progressive shifts: as the therapy's limitations became more apparent, the theory became more expansive, and extended itself beyond its beginnings in neurotic symptoms, and into slips, dreams, character formation, and sociology. In short, it encompassed more of normal behavior as its expectations for the therapy of pathological behavior were increasingly called into question. The paper explores some implications of this historical turn for a scientific data base with opportunities to test and revise the various psychoanalytic hypotheses. One view would have it that psychoanalysis has been lamed by the physicalistic language of its metapsychology, by its isolation from the neurosciences and the cognitive sciences, and by a compartmentalization of practice and knowledge that has kept its practitioners focused on the worried well and unimpressed by the knowledge at its borders. Another view would propose that the restiveness of some current and past theorists to claim the mantle of "science" continues to lead to premature and awkward attempts to couple psychoanalysis with putative neighbors rather than stick to its last of shaping its own findings into a language reflecting a coherent theory capable of validation.

Some pros and cons of computer-assisted psychotherapy.

We briefly describe a method of short-term computer-assisted psychotherapy for stress-related conditions and then reply to a number of objections to the method that have been voiced by professional colleagues.