Open field activity and avoidance behavior following serotonin depletion: a comparison of the effects of parachlorophenylalanine and electrolytic midbrain raphe lesions

Abstract

Three experiments were performed in order to compare the behavioral effects of electrolytic destruction of the dorsal and median mesencephalic raphe nuclei (MR lesion) and parachlorophenylalanine (pCPA; 300 mg/kg, IP) administration. Forebrain 5-hydroxytryptamine (5-HT) was measured in all animals following completion of behavioral testing. In the first experiment open field behavior (one 50 min session) and two-way (shuttle) conditioned avoidance acquisition (50 massed trials) were examined 68-72 hr after vehicle or pCPA administration in rats which had received control operations or MR lesions two weeks earlier. Only the MR lesion and the MR lesion + pCPA groups evidenced increased open field activity and facilitated two-way avoidance learning. Although the reduction in forebrain 5-HT of the pCPA group (85%) was greater than in the MR lesion group (55%), the pCPA treated animals did not differ from the control group. In the second experiment animals were tested in the open field 24, 48 or 72 hr after pCPA treatment to determine its effects on activity level as a function of the time after injections. No differences between the vehicle and pCPA groups, however, were found. In the third experiment, the effects of pCPA (72 hr postinjection) on the acquisition of an unsignalled one-way avoidance response was examined. MR lesion rats tested in the same apparatus and with the same procedure repeatedly have been shown to be impaired in this task. The pCPA and vehicle animals, however, did not differ. Reduction in 5-HT following electrolytic MR lesions and pCPA administration, thus, produce different behavioral effects. MR lesions, but not pCPA treatment, result in (1) increased activity in a novel environment, (2) facilitated two-way conditioned avoidance learning, and (3) impaired acquisition of an unsignalled one-way avoidance response. These data support earlier studies suggesting that the behavioral effects of electrolytic MR lesions are not due primarily to their disruption of ascending 5-HT pathways. The role of 5-HT in avoidance conditioning and the regulation of activity level, furthermore, remains to be elucidated.