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1.
J Neural Transplant ; 1(1): 23-31, 1989.
Article in English | MEDLINE | ID: mdl-2535266

ABSTRACT

Rats which receive injections of kainic acid (KA) into the striatum show many of the anatomical, biochemical and behavioral abnormalities seen in patients with Huntington's disease. Recently, it has been reported that fetal striatal transplants into the lesioned striatum could normalize the neurological and behavioral abnormalities produced by the KA lesion. The present study examined the issue of transplant integration in producing behavioral recovery. In one experiment, lesioned animals with transplants located within the lateral ventricle were compared against parenchymally transplanted rats. It was found that unless the ventricular transplant grew into the lesioned striatum there was no recovery. The second experiment demonstrated that electrolytic destruction of a successful fetal striatal transplant could reverse the transplant-induced behavioral recovery. These results suggest that the integrity of the transplant is important in maintaining behavioral recovery. A continuing functional interaction between the host brain and transplanted tissue may be a vital element in the success of the fetal striatal transplant.


Subject(s)
Brain Tissue Transplantation/physiology , Corpus Striatum/transplantation , Huntington Disease/surgery , Motor Activity , Analysis of Variance , Animals , Disease Models, Animal , Electroshock , Huntington Disease/physiopathology , Kainic Acid , Male , Rats , Rats, Inbred Strains
2.
Psychopharmacology (Berl) ; 99(1): 60-3, 1989.
Article in English | MEDLINE | ID: mdl-2506605

ABSTRACT

Most investigators have found a decrease in emotional defecation in rats given neuroleptics in novel environments, supporting their action as a major tranquilizer. We have found, however, that in rats a profound increase in emotional defecation can result from neuroleptic administration in well habituated environments, such as the homecage. Anticholinergics are known to be effective in treating the side effects associated with neuroleptic administration in humans. Therefore the present study determined the effects of anticholinergic treatment in this animal model. In male rats, defecation was measured for a 1-h test period in their homecage following various doses of the central and peripheral anticholinergics, scopolamine, and n-methylscopolamine, respectively. A decrease in fecal excretions and an attenuation of haloperidol-induced defecation was found following administration of scopolamine. n-Methylscopolamine reduced defecation at all doses. When n-methylscopolamine was combined with haloperidol, both fecal mass and number decreased significantly. Since both anticholinergic agents reduced haloperidol-induced defecation it is suggested that their effectiveness is mediated through peripheral mechanisms.


Subject(s)
Defecation/drug effects , Emotions/drug effects , Haloperidol/pharmacology , Scopolamine/pharmacology , Animals , Male , N-Methylscopolamine , Parasympathetic Nervous System/physiology , Rats , Rats, Inbred Strains , Scopolamine Derivatives/pharmacology
3.
Brain Res ; 446(1): 183-8, 1988 Apr 12.
Article in English | MEDLINE | ID: mdl-2967100

ABSTRACT

Striatal kainic acid (KA) lesions induce behavioral and biochemical deficits which resemble symptoms encountered in patients suffering from Huntington's disease. In rats with KA lesions, fetal striatal transplants have shown to reverse the pervasive nocturnal hyperactivity induced by the lesion. In the present study 4.6 mm3 of fetal striatal tissue were delivered bilaterally into the anterodorsal portion of the lesioned caudate nucleus. Care was taken to deliver the transplant within the host parenchyma and away from the lateral ventricles. Locomotor behavior analyzed using the Digiscan animal activity monitors before and after the transplants demonstrated a reversal of the hyperactivity following transplants in 70% of lesioned animals. Microinjections of horseradish peroxidase delivered into the globus pallidus and substantia nigra of a small group of functionally recovered transplanted animals, did not reveal evidence for reinnervation between host nigra or pallidum and the transplant at 10 weeks post-transplantation. Other laboratories have reported anatomical connections by 6 months post-transplantation. Ventricular/brain ratios demonstrated that intraparenchymal transplants significantly reduced the ventricular dilation following KA lesion. These results suggest that functional recovery can be obtained when the transplant is immersed into the host's striatal parenchyma regardless of the existence of long-range anatomical connections.


Subject(s)
Corpus Striatum/transplantation , Animals , Corpus Striatum/pathology , Disease Models, Animal , Fetus , Huntington Disease/physiopathology , Huntington Disease/therapy , Kainic Acid , Motor Activity , Rats
4.
Pharmacol Biochem Behav ; 27(3): 583-6, 1987 Jul.
Article in English | MEDLINE | ID: mdl-3659084

ABSTRACT

It is well established that embryonic tissue transplantation into an abnormal or lesioned brain can ameliorate some of the accompanying symptomatology. Specifically, transplants placed into kainic acid (KA) or ibotenic acid lesioned striatal rats promote behavioral recovery in various ambulatory measures. In the KA animal model, when the transplant encroached on normal host tissue, the behavioral recovery was diminished. However, little has been done to reveal what effect tissue transplants have on normal host brain. The present study placed E-17 striatal tissue into a normal adult striatum. Digiscan locomotor testing revealed that ten weeks after surgery, the implanted animals demonstrated pervasive nocturnal hyperactivity. Ambulatory, vertical and stereotypic measures were significantly increased when compared to controls. Rats with ten week implants showed lower increases in body gain yet increased food consumption when compared to controls. The transplants survived and contained normal looking AChE positively stained neurons. Evidence for fiber passage through the host-graft interface was also seen. When comparing three and ten week implants, there was a decrease in transplant size in the latter group accompanied by enlarged ventricles giving the brain a lesioned-like appearance. From these results, it is suggested that the placement of E-17 striatal tissue into adult striatum results in lesion-like behavior which may be attributed to the physical disruption of striatal systems.


Subject(s)
Corpus Striatum/transplantation , Motor Activity/physiology , Acetylcholinesterase/analysis , Animals , Body Weight , Corpus Striatum/enzymology , Corpus Striatum/physiology , Feeding Behavior/physiology , Histocytochemistry , Male , Rats , Rats, Inbred Strains , Time Factors
5.
Behav Neurosci ; 101(1): 131-3, 1987 Feb.
Article in English | MEDLINE | ID: mdl-3828051

ABSTRACT

The increased locomotor activity induced by systemic injections of d-amphetamine or scopolamine in rats was studied in Digiscan Animal Activity Monitors. This multifactorial analysis of locomotion demonstrated that activity measures of horizontal (ambulatory), vertical (rearing), stereotypic, and rotational behaviors differed depending on dose and drug. The topographies of these activity variables may be unique for the dopaminergic and cholinergic systems underlying hyperactivity. These results are a first step toward a needed increase in the sophistication of behavioral pharmacological techniques, allowing for the development of specific activity prints for different classes of psychoactive agents.


Subject(s)
Arousal/drug effects , Dextroamphetamine/pharmacology , Motor Activity/drug effects , Scopolamine/pharmacology , Animals , Basal Ganglia/drug effects , Dose-Response Relationship, Drug , Male , Rats , Rats, Inbred Strains , Stereotyped Behavior/drug effects
6.
Psychopharmacology (Berl) ; 91(1): 45-9, 1987.
Article in English | MEDLINE | ID: mdl-2881319

ABSTRACT

The neuroleptic haloperidol was found to produce increased defecation in laboratory rats when tested in well habituated environments. It is well known that haloperidol induces catalepsy through antagonism of striatal dopaminergic receptor mechanisms. When another cataleptic agent, morphine, was tested, no significant increases in defectation were detected. Another study focused on the possible role of peripheral dopamine receptor sites within the gastrointestinal tract on neuroleptic-induced defecation. When the peripheral dopamine receptor antagonist domperidone was tested, no significant differences in fecal elimination were recorded. Thus, it appeared that the cataleptic state per se, or the peripheral effects of haloperidol did not seem to be responsible for the increased defecation. Defection is often used as an index of emotionality. The fact that this measure increased following administration of a major tranquilizer suggested the need to study more directly the relationship of this phenomenon of defecation with the affective state of the animal. In a control study it was found that the antianxiety agent benzodiazepam did not by itself influence defecation. However, those animals which were pre-injected with diazepam followed by haloperidol did not show increased defecation. Thus under certain circumstances, normal rats given haloperidol show "emotional defecation" which seems to reflect increased anxiety. This finding may serve as a basis for the development of an animal model for some of the atypical side effects of major tranquilizers, such as akathisia, dysphoria, and neuroleptic anxiety syndrome.


Subject(s)
Antipsychotic Agents/adverse effects , Anxiety/chemically induced , Defecation/drug effects , Disease Models, Animal , Haloperidol/pharmacology , Animals , Corpus Striatum/drug effects , Digestive System/drug effects , Eliminative Behavior, Animal , Male , Rats , Rats, Inbred Strains , Receptors, Dopamine/drug effects , Syndrome
7.
Brain Res ; 367(1-2): 314-8, 1986 Mar 05.
Article in English | MEDLINE | ID: mdl-3697706

ABSTRACT

Kainic acid-induced lesions (KAL) of the striatum produce body weight and regulatory deficits in the rat. Unlike lateral hypothalamic rats. KAL rats drink more during food deprivation and eat more afterwards as compared to both baseline conditions and control rats. The present study investigated these effects further. As in previous studies, food deprivation was found to cause polydipsia and increased postdeprivational food intake in the KAL animal. Urination and defecation, often used as an index of emotionality, were also found to increase under these conditions. When the antidiuretic hormone vasopressin was injected, all of these differences remained with the exception of postdeprivational feeding--KAL rats no longer ate more than controls. These findings suggest that psychogenic factors--but not hormonal influences--may play a primary role in the regulatory peculiarities seen in the KAL rat.


Subject(s)
Corpus Striatum/drug effects , Drinking Behavior/drug effects , Emotions/drug effects , Feeding Behavior/drug effects , Kainic Acid/pharmacology , Animals , Defecation/drug effects , Diuresis/drug effects , Eliminative Behavior, Animal/drug effects , Male , Rats , Rats, Inbred Strains , Vasopressins/pharmacology
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