Studies on the possible role of brain 5-HT systems and adrenocortical activity in behavioural responses to nicotine and diazepam in an elevated X-maze.

Subchronic (6 days) but not acute injections of nicotine (0.4 mg/kg SC) increased spontaneous activity (P less than 0.01) in an elevated X-maze composed of two open and two enclosed runways. Neither acute nor subchronic nicotine altered significantly the ratio of open:enclosed runway entries (O/E ratio). Diazepam (5 mg/kg PO) had no significant effects on spontaneous activity but increased the O/E ratio (P less than 0.05). Acute nicotine increased (P less than 0.01) whereas subchronic nicotine caused a small decrease (P less than 0.05) in the plasma corticosterone concentration. Both acute and subchronic diazepam decreased the levels of the hormone (P less than 0.01 and P less than 0.05, respectively) although the reduction elicited by chronic diazepam was less than that caused by acute diazepam (P less than 0.05). In the experiments with diazepam the plasma corticosterone concentration correlated negatively with the O/E ratio (r = -0.58; P less than 0.05), whereas in the experiments with nicotine plasma corticosterone correlated negatively (r = -0.46; P less than 0.05) with enclosed runway entries. Nicotine injections were associated with a regionally-selective reduction in the 5-hydroxyindole acetic acid (5-HIAA) concentration in the hippocampus (P less than 0.05) and a reduction in hippocampal 5-hydroxytryptamine (5-HT) which approached statistical significance. Chronic, but not acute, diazepam increased (P less than 0.01) hypothalamic 5-HT. The changes in 5-HT and 5-HIAA did not appear to be directly related to the behavioural or adrenocortical responses to either of the drugs.