Brain Research, 89 (1975) 303-325 ,~'~ Elsevier Scientific Pubhshmg Company, Amsterdam - Printed m The Netherlands
BEHAVIORAL EFFECTS IN T H E R A T
OF SELECTIVE M I D B R A I N
RAPHE
303
LESIONS
BOLEK SREBRO AND STANLEY A. LORENS
blstttutes of Physiology and Psychology, and DepaJtment of Pharmacology, UmverstO' oJ Bergen. Bergen (Norway) (Accepted January 7th, 1975)
SUMMARY
Lesions were produced in the median (n =- 8), dorsal (n = 7) or both (n = 7) mldbrain raphe nuclei and their effects on behavior (days 16-54 postoperatwely) compared to that of controls (n = 9). In addition, forebrain 5-hydroxytryptamme (5-HT) concentrations were determined. Only the median and combined lesion groups showed increased running wheel and open field activity, as well as enhanced reactivity to novel stimuli and environmental change None of the lesion groups, however, showed changes in home cage activity on postoperative day 21. Although all lesion groups were deficient in the acquisition and retention of oneway avoidance, the deficits were of a greater magnitude in the median and combined lesion groups. The latter two groups, furthermore, were impaired in forced extinction of the one-way avoidance response, but only the combined lesion group evidenced facilitation of two-way avoidance acquisition. Thus, in contrast to the effects of median or combined raphe lesions, lesions in the dorsal raphe nucleus affected few of the behavioral parameters studied These results suggest that the dorsal raphe nucleus plays a different behavioral role than the median raphe nucleus The median nucleus appears to be revolved in the regulation of activity level, the reaction to novelty and environmental change, and the response to averswe stimuli Possible mechanisms for the observed behavioral changes are discussed, as well as their apparent slmdarity to the effects of other mesencephahc and limbJc lesions. Lastly, the median, dorsal and combined raphe lesions lowered forebram 5-HT by 26, 65, and 77 ~ , respectively, versus controls. These reductions differed significantly from each other, and with prewously reported data indicate that the dorsal raphe nucleus is the principal origin of forebrain 5-HT. It is suggested, further-
304 more, that the behavmral effect~ of m~dbrain raphe lesmns are not due prmmr~lv to their associated reductmns m forebram 5-HT
INTRODUCTION
The dorsal and median raphe nuclei he within what Nauta 4s has termed the 'limbic-mldbrain area', a region reciprocally connected, principally via the medial forebrain bundle, with hypothalamic and limbic-forebrain structures2,S,s, 11,46. Recent interest in these mldbrain raphe nuclei, however, derives primarily from their identification as the 5-hydroxytryptamine (5-HT) containing B7 and B8 cell group~ la Although a large number of p e n k a r y a within these raphe nuclei do not contain 5-HT 4.26,5", the effects of lesions m these nuclei have been viewed as a means of specifically depleting forebrain 5-HT without affecting peripheral 5-HT or other monoammes, a problem encountered w~th the administratmn of such drugs as parachlorophenylalamne (p-CPA), reserpine, and the monoamlne oxidase mhlbltors Thus, the effects of raphe lesions have been studied to assess the role of 5-H]- m sleep 29, acnwty level 27,a4,42,47,6°,6t, habituation t4, aggression 22,60,61, pare sens~t~v~t:y and morphine analgesia
BEHAVIORAL EFFECTS IN T H E R A T
OF SELECTIVE M I D B R A I N
RAPHE
303
LESIONS
BOLEK SREBRO AND STANLEY A. LORENS
blstttutes of Physiology and Psychology, and DepaJtment of Pharmacology, UmverstO' oJ Bergen. Bergen (Norway) (Accepted January 7th, 1975)
SUMMARY
Lesions were produced in the median (n =- 8), dorsal (n = 7) or both (n = 7) mldbrain raphe nuclei and their effects on behavior (days 16-54 postoperatwely) compared to that of controls (n = 9). In addition, forebrain 5-hydroxytryptamme (5-HT) concentrations were determined. Only the median and combined lesion groups showed increased running wheel and open field activity, as well as enhanced reactivity to novel stimuli and environmental change None of the lesion groups, however, showed changes in home cage activity on postoperative day 21. Although all lesion groups were deficient in the acquisition and retention of oneway avoidance, the deficits were of a greater magnitude in the median and combined lesion groups. The latter two groups, furthermore, were impaired in forced extinction of the one-way avoidance response, but only the combined lesion group evidenced facilitation of two-way avoidance acquisition. Thus, in contrast to the effects of median or combined raphe lesions, lesions in the dorsal raphe nucleus affected few of the behavioral parameters studied These results suggest that the dorsal raphe nucleus plays a different behavioral role than the median raphe nucleus The median nucleus appears to be revolved in the regulation of activity level, the reaction to novelty and environmental change, and the response to averswe stimuli Possible mechanisms for the observed behavioral changes are discussed, as well as their apparent slmdarity to the effects of other mesencephahc and limbJc lesions. Lastly, the median, dorsal and combined raphe lesions lowered forebram 5-HT by 26, 65, and 77 ~ , respectively, versus controls. These reductions differed significantly from each other, and with prewously reported data indicate that the dorsal raphe nucleus is the principal origin of forebrain 5-HT. It is suggested, further-
304 more, that the behavmral effect~ of m~dbrain raphe lesmns are not due prmmr~lv to their associated reductmns m forebram 5-HT
INTRODUCTION
The dorsal and median raphe nuclei he within what Nauta 4s has termed the 'limbic-mldbrain area', a region reciprocally connected, principally via the medial forebrain bundle, with hypothalamic and limbic-forebrain structures2,S,s, 11,46. Recent interest in these mldbrain raphe nuclei, however, derives primarily from their identification as the 5-hydroxytryptamine (5-HT) containing B7 and B8 cell group~ la Although a large number of p e n k a r y a within these raphe nuclei do not contain 5-HT 4.26,5", the effects of lesions m these nuclei have been viewed as a means of specifically depleting forebrain 5-HT without affecting peripheral 5-HT or other monoammes, a problem encountered w~th the administratmn of such drugs as parachlorophenylalamne (p-CPA), reserpine, and the monoamlne oxidase mhlbltors Thus, the effects of raphe lesions have been studied to assess the role of 5-H]- m sleep 29, acnwty level 27,a4,42,47,6°,6t, habituation t4, aggression 22,60,61, pare sens~t~v~t:y and morphine analgesia
