Kitamura, Yoshihisa

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis induces hyperglycemia and serotonin (5-HT)2A receptor supersensitivity. In the present study, to investigate the effect of hyperglycemia on the function of 5-HT2A receptors, we compared the 5-HT2A receptor-mediated wet-dog shake responses in rats treated with adrenocorticotropic hormone (ACTH), dexamethasone and streptozotocin. ACTH (100 μg/rat per day, s.c.), dexamethasone (1 mg/kg per day, s.c.) and streptozotocin (60 mg/kg, i.p.) produced significant hyperglycemia at 14 days after the start of these treatments, and the hyperglycemia was most pronounced in the streptozotocin-treated rats. The wet-dog shake responses induced by (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A receptor agonist, were significantly enhanced at 14 days after repeated treatment with ACTH and dexamethasone. However, streptozotocin-induced diabetes had no effect on the wet-dog shake responses. The results of the present study suggest that hyperglycemia is not strongly associated with the enhanced susceptibility of 5-HT2A receptors under the condition of hyperactivity of the HPA axis.

We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shortened significantly. From the viewpoint of imipramine's effect, these findings suggest that chronic forced-swim stress testing in rats may be an effective animal model for depression.

It is well known that priming stimulation promotes the motivational effects of intracranial self-stimulation(ICSS) behavior. An experimental methodology using the runway method could separately study the reward and motivational effects of ICSS behavior. In the present study, we examined the motivational effect of nicotine as measured by the runway method using priming stimulation of ICSS behavior. Electrodes were implanted chronically into the medial forebrain bundle (MFB) in rats. A lever for stimulation of the MFB was set on the opposite side of the start box in the apparatus, and rats were trained to get a reward stimulation (50-200 microA, 0.2 ms, 60 Hz) of MFB when the goal lever was pressed. After the rats were trained to press the lever, a priming stimulation of the MFB was performed. After receiving the priming stimulation, rats were placed at the start box of the runway apparatus, and the running time duration until the goal lever was pressed was measured. Subcutaneous injection of nicotine at a dose of 0.2mg/kg produced an increase in running speed to obtain the reward stimulation, and priming stimulation facilitated the motivational effect to obtain the electrical brain stimulation reward in the rats. These results suggest that nicotine significantly enhanced the motivational effect on ICSS behavior as determined using the runway method. The runway method using priming stimulation of ICSS behavior may become the new experimental methodology with which to measure the motivational effect of some drugs.