Although selective 5-hydroxytryptamine (5-HT) reuptake inhibitors (SSRIs) are widely used in the chronic treatment of several anxiety disorders, increased anxiety has been observed in some patients at the beginning of treatment with these compounds. Similar increases in anxiety-related behaviors have been observed in animal studies following a single injection with SSRIs. The mechanism underlying this effect is unclear. The aim of the present study was to investigate the effects of a variety of psychoactive compounds on the anxiogenic-like activity of fluoxetine. The drugs used included the benzodiazepine diazepam, the 5-HT1A receptor partial agonist buspirone, the 5-HT1A receptor antagonists pindolol and WAY-100635, the non-selective 5-HT2 receptor antagonists methiothepin, mianserin and ritanserin, the non-selective dopamine (DA) receptor antagonist haloperidol, the D1 antagonist SCH23390, the selective D2 antagonist raclopride, the D2/3 agonist quinelorane, the cholecystokininB (CCK(B)) receptor antagonist LY 288513, and the corticotropin-releasing factor1 (CRF1) receptor antagonist CP-154,526. Experiments were performed in the free-exploration test. This model is based on the strong neophobic reactions exhibited by BALB/c mice when confronted simultaneously with a familiar and a novel environment. When administered alone, diazepam (1 and 2 mg/kg), buspirone (1 mg/kg) and mianserin (0.3 mg/kg) produced anxiolytic-like effects as they significantly increased exploratory activity of the novel compartment. In contrast, fluoxetine (20 mg/kg) almost completely suppressed exploration of the novel area. Diazepam reversed the anxiogenic-like as well as the locomotor impairment induced by fluoxetine, while quinelorane blocked only the anxiogenic action of fluoxetine. None of the other compounds was able to counteract this effect. Taken together, these results suggest that dopaminergic mechanisms may underlie, at least in part, the behavioral effects of fluoxetine in the free-exploration test, whereas 5-HT1A 5-HT2, CCK(B) and CRF1 receptors may not be involved primarily in these effects.

No abstract

In rodents, chronic dietary alpha-linolenic acid deficiency decreases learning and memory and alters dopaminergic and serotoninergic neurotransmission. However, these two neurotransmitter systems are related mainly to attention, emotion and locomotion. Therefore, we decided to investigate the effects of dietary alpha-linolenic acid deficiency in rats tested with animal models of distractibility (the distractometer procedure), anxiety (the elevated plus maze) and ambulatory activity (a circular corridor). Moreover, because these neurochemical modifications persist during aging, we decided to study the effects of aging on these behaviors by using rats aged 2, 6, 12 and 24 mo. An age-related decline in distractibility was observed that was accelerated by linolenic acid deficiency. Indeed, an age-related reduction in distractibility was found in so far as distraction time was reduced at the age of 12 mo in controls and at the age of 24 mo in deficient groups compared with 2-mo-old rats. Moreover, distraction time was significantly lower in 6- and 24-mo-old rats fed a deficient diet compared with age-matched controls. Anxiety was not modified by diet or age. Finally, a parallel decrease in locomotion was exhibited by rats fed both diets between 6 and 12 mo of age. Locomotion was not modified by diet. These results show that dietary alpha-linolenic deficiency alters behavior in a very specific way; distractibility is modified by diet, whereas anxiety and locomotion are not, suggesting that particular brain areas may be altered.

No abstract

An open field choice test was used to determine whether maternal deprivation enhanced the motivation to stay close to the mother. Pups could choose between the dam, 3 sisters and 3 unknown animals of the same age. In addition, an empty enclosure identical to those that contained the stimulus animals were present as a nonsocial choice. Rats that were separated from their mother at 20 days of age and tested about 13 h later were compared to animals that had stayed with the mother until just before the test. It was found that maternal separation increased the time spent close to the mother and reduced that spent close to strangers or an empty enclosure. In fact, weaned animals spent far more time close to the mother than they spent close to any other available choice. Moreover, the mean duration of visits to the mother was much increased during the latter half of the 60-min test. These data were interpreted as showing that the mother had rewarding properties, and that maternal deprivation increased her reward value. In further experiments, the role of opioids for this increase in reward value was evaluated. Morphine enhanced the time spent close to the mother, but only in animals that had been subjected to maternal deprivation for about 13 h. Naloxone had the opposite effect. These data show that the mother''s reward value is altered when the activity of opioid systems is modified. It is suggested that the mother acquires rewarding properties because of association with nutritive suckling-induced opioid release.