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

Abstract

Subchronic (6 days) but not acute injections of nicotine (0.4 mg/kg SC) increased spontaneous activity (P<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<0.05). Acute nicotine increased (P<0.01) whereas subchronic nicotine caused a small decrease (P<0.05) in the plasma corticosterone concentration. Both acute and subchronic diazepam decreased the levels of the hormone (P<0.01 and P<0.05, respectively) although the reduction elicited by chronic diazepam was less than that caused by acute diazepam (P<0.05). In the experiments with diazepam the plasma corticosterone concentration correlated negatively with the O/E ratio (r=−0.58; P<0.05), whereas in the experiments with nicotine plasma corticosterone correlated negatively (r=−0.46; P<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<0.05) and a reduction in hippocampal 5-hydroxytryptamine (5-HT) which approached statistical significance. Chronic, but not acute, diazepam increased (P<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.