Hippocampal lesions, haloperidol, and excessive grooming

Abstract

Rats with bilateral hippocampal damage, neocortical lesions, or sham operations were tested for excessive grooming after intracerebroventricular (icv) injection of ACTH'-14 or saline. The animals were tested for 3 days after pretreatment with low doses of haloperidol and on the first and last test days after saline pretreatment. The animals with hippocampal lesions evidenced less grooming than did the other groups, after both icy ACTH and icy saline. In addition, their grooming was reduced to a greater extent by low doses of haloperidol than was grooming by controls. This was interpreted to reflect altered dopaminergic sensitivity after hippocampal destruction.Animals with near-total bilateral hippocampal destruction have been shown to exhibit an altered responsiveness to agents with selective effects on dopaminergic systems (see Isaacson, 1980, for a review) and also to reduce the excessive grooming produced by intraventricular injection of ACTH'.24 (Colbern, Isaacson, Bohus, & Gispen, 1977;Elstein, Hannigan, & Isaacson, 1981). Furthermore, both systemic and intraventricular injections of the dopaminergic blocking agent haloperidol, can antagonize both ACTH-induced grooming and that produced by the circumstances related to testing in a novel environment (see Gispen & Isaacson, 1981, for a review). However, the doses of systemically administered haloperidol required to produce a reduction in excessive grooming have been high, typically of the order of 2 mg/kg. The present study was undertaken to extend our knowledge of the mechanisms of action of the neuropeptides by determining whether lower doses would produce an effect on ACTH-induced excessive grooming in animals with hippocampal damage or in control subjects. The paradigm chosen was one in which the lesions of the hippocampus or surgical control procedures were made at the same time cannula guides were implanted into the foramen of Monro (the interventricular foramen). The animals were tested for peptide-induced excessive grooming at various postsurgical times after pretreatment with haloperidol.Male Long-Evans hooded rats received sham operations, neocortical damage, or neocortical and hippocampal destruction by aspiration as described by Isaacson and Woodruff (1975). At the time of central nervous system damage, polyethylene cannula guides were implanted into the intraventricular foramen according to the procedures of Brakkee, Weigant, and Gispen (1979). Behavioral tests for grooming were given on the 5th, 7th, 9th, 11 th, and 14th days after surgery (Tests 1, 2, 3, 4, and 5, respectively) following the procedure of Gispen, Wiegant, Greven, and de Wied (1975). Different sets of animals were given intracerebroventricular (icv) injections of either 2 /Ag of ACTH'.24 in 2 /AI of saline or 2 /AI of saline on every test day. Pretreatments with progressive doses of haloperidol (.01, .04, or .08 mg/kg) were given ip on Test Days 2,3, and 4. These were given 10 min before the icv injection. A saline pretreatment was given ip on Test Days 1 and 5. After the final ...

ACTH and Grooming Behaviour in the Rat

“…In addition, Bar et al (1981) observed that the hippocampal destruction led to a suppression of novelty-induced grooming immediately after exposure to novelty, but water immersion induced a normal grooming response. Isaacson and Colbern (1981) found that the dopamine receptor-blocker haloperidol was more effective in reducing ACTH-induced excessive grooming in hippocampectomized rats than in sham-operated control rats. This finding was interpreted to reflect altered dopaminergic sensitivity after hippocampal destruction and to confirm the involvement of dopaminergic systems in ACTH-induced grooming (see Sect.…”