Anterior thalamus deep brain stimulation at high current impairs memory in rats.

Deep brain stimulation (DBS) of the anterior thalamic nucleus (AN), an important relay in the circuitry of memory, is currently being proposed as a treatment for epilepsy. Despite the encouraging results with the use of this therapy, potential benefits and adverse effects are yet to be determined. We show that AN stimulation at relatively high current disrupted the acquisition of contextual fear conditioning and impaired performance on a spatial alternating task in rats. This has not been observed at parameters generating a charge density that approximated the one used in clinical practice. At settings that impaired behavior, AN stimulation induced a functional depolarization block nearby the electrode, increased c-Fos expression in cerebral regions projecting to and receiving projections from the AN, and influenced hippocampal activity. This suggests that complex mechanisms might be involved in the effects of AN DBS, including a local target inactivation and the modulation of structures at a distance. Though translating data from animals to humans has to be considered with caution, our study underscores the need for carefully monitoring memory function while selecting stimulation parameters during the clinical evaluation of AN DBS.

Effects of nociceptin/orphanin FQ in the acquisition of contextual and tone fear conditioning in rats.

Nociceptin, or orphanin FQ (N/OFQ), the endogenous ligand of NOP receptors, is known to regulate learning and memory processes. To verify the role of N/OFQ in the acquisition of contextual (CFC) and tone fear conditioning (TFC), Wistar male rats received intracerebroventricular injections of N/OFQ (0.1-5.0 nmol) before training, and were tested 24 and 48 hr later to access the freezing response to context and tone, respectively. The intermediate doses (1.0 and 2.5 nmol) impaired the CFC test, sparing TFC. The highest dose (5.0 nmol) reduced freezing during both tests, a result that may be due to nonspecific effects. The posttraining injection of N/OFQ (1 or 5 nmol) did not interfere with CFC and TFC, suggesting a specific effect of the peptide in acquisition processes. Moreover, the impairment observed with N/OFQ (1 nmol) in CFC cannot be attributed to a state-dependent learning because it was not reversed by its pretest administration. The data support the negative role of N/OFQ in the acquisition of aversively motivated tasks, which encompass a spatial component and depend on the hippocampus.