PCPA-PRODUCED EFFECTS ON BEHAVIOR IN RATS
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HarreIl and Balagura, 1975; Hynes et al., 1975; Lanierer al., 1974). The
interpretations of these changes in the behavioral consequences of brain
damage are varied but include the reduction of norepinephrine released
near the site of the damage (Osterholm and Mathews, 1972a,b) and the
induction of a chemical supersensitivity in certain remaining systems
prior to the induction of additional supersensitivity produced by the lesion
itself (Glick and Greenstein, 1974). The present study was undertaken to
determine if a reduction in serotonin (5-HT) activity would provide any
relief from the usual effects Ofhippocampal damage using an experimental
procedure similar to that used by Lanier et al. (1974). In that study
animals pretreated with AMT prior to bilateral hippocampal destruction
had a less extreme passive avoidance deficit than those not given AMT,
although the locomotor hyperactivity that develops about 1 week post-
Operatively was not affected by the AMT pretreatment. Changes in the
usual consequences of hippocampal damage after prior serotonin deple-
tion would also be of interest because of the possibility that the presence
of 5-HT in Catecholaminergic neurons may be responsible for their capa-
bility for sprouting (Berry and Riches, 1974).
The adminstration of p-chlorophenylalanine (PCPA) depletes 5-HT
content of the brain by interfering with the enzyme, tryptamine hy-
droxylase (Koe and Weissman, 1966; Weissman, 1973). This prevents the
synthesis of serotonin. In the present study, rats were treated with PCPA
for 3 days prior to receiving bilateral hippocampal or neocortical lesions.
Testing for changes in locomotor activity in the open field started im-
mediately after surgery. Ten open field tests were conducted over the
subsequent 2 weeks. During the testing in the open field, grooming and
rearing behavior were also recorded. After the testing in the open field,
the rats were trained on a passive avoidance task.
On the basis of three 5-min preoperative tests performed on consecu-
tive days in the open field, 43 male Long-Evans hooded rats from Charles
River Farms were divided into six groups with approximately equivalent
mean activity scores. Intraperitoneal injections of an aqueous suspension
of PCPA (100 mg∕kg at 10 mg∕ml each day, total of 300 mg∕kg) were given
to nine rats that were to receive bilateral hippocampal ablations (Group
Hp), six rats that were to receive bilateral neocortical lesions (group Np)
and to eight intact, normal rats (Group Cp). Saline (pH corrected) injec-
tions were given to an additional eight rats that were to receive hip-
pocampal ablation (Group He), to four rats that were to receive neocorti-
cal lesions (Groiip Ne), and to seven intact rats (Group Ce). These
injections were given in the morning of 3 consecutive days immediately
following the preoperative activity test and before the day of surgery.
These dose levels of PCPA have been shown to block the synthesis of
5-HT (Koe and Weissman, 1966) and reduce the levels of serotonin by
over 80% of controls.
All rats, including unoperated controls, were given 50 mg∕kg of sodium