Alan E. Fisher

Tail pinch-induced eating, gnawing and licking behavior in rats: Dependence on the nigrostriatal dopamine system

Mild-tail-pinch induces a syndrome of eating, gnawing and licking behavior in rats in the presence of food. Detailed behavioral, pharmacological and biochemical analyses of this phenomenon resulted in the following conclusions. (1) This is an unusually reliable phenomenon, demonstrable in each of more than 200 animals tested. (2) Eating is by far the predominant response to tail-pinch. (3) Tail-pinch behavior is critically dependent on the nigrostriatal dopamine system. (4) There are striking pharmacological parallels between tail-pinch behavior and schizophrenia.

Cholinergic Tracing of a Central Neural Circuit Underlying the Thirst Drive

Cholinergic stimulation of any of a number of interrelated limbic and diencephalic structures in the rat elicits a rapid and marked increase in water intake. We postulate that a generalized Papez circuit mediates the thirst drive, that the circuit is specifically and functionally sensitive to cholinergic action, and that other primary drives depend on closely parallel neural circuits partitioned both structurally and biochemically.

Ventricular obstruction: effect on drinking induced by intracranial injection of angiotensin

Lesions of the subfornical organ (SFO) severely attenuated drinking induced by injections of angiotensin II into the lateral ventricles, but a few days (4 to 14) later a recovery of the drinking response is observed. A possible explanation for this is that other dipsogenic sites are involved which are beyond the interventricular foramen and that SFO lesions produce an obstruction by edema or debris at the foramen which blocks access of cerebrospinal fluid-borne angiotensin to those sites. This hypothesis is supported by tracer studies and by direct injection into the third ventricle of SFO-lesioned animals. Other studies reported implicate the anteroventral third ventricle as a likely site for angiotensin receptors.

Neurochemical mediation of reward: A significant role for dopamine? ☆

Abstract Intraventricular injection of 6-hydroxydopamine resulted in only a temporary decrement of self-stimulation. Treatment with the alpha-adrenergic receptor blocking agent, phentolamine, had virtually no effect on self-stimulation in either 6-hydroxydopamine treated or normal rats; whereas haloperidol, a dopamine receptor blocking agent, markedly reduced self-stimulation in normal rats. Treatment with FLA-63, a potent inhibitor of dopamine-beta-hydroxylase, had no effect on self-stimulation but very significantly reduced eating. These results imply that dopamine may be importantly involved in the mediation of positive reinforcement and/or that the role of norepinephrine may be a minor one.

Anteroventral third ventricle site of action for angiotensin induced thirst

The central site of action for angiotensin induced thirst was investigated in rats. Subfornical organ lesions resulted in a temporary abolition of drinking induced by lateral preoptic or lateral ventricle microinjections of angiotensin but drinking to anteroventral third ventricle microinjections of angiotensin (or carbachol) was unaffected. Drinking to elevated systemic levels of angiotensin was attenuated but not abolished by subfornical organ lesions. When spread of injected angiotensin via cerebrospinal fluid circulation was controlled by placing plugs at selected locations in the ventricles, drinking was elicited only when intracranial microinjections of angiotensin gained access to anteroventral third ventricle. It was concluded that subfornical organ is not the exclusive dipsogenic receptor for angiotensin, rather angiotensin exerts at least part of its dipsogenic effect by spread through the ventricular system to receptors in the vicinity of the anteroventral third ventricle.

Selective cholinergic neurotoxin: AF64A's effects in rat striatum

The selective neurotoxic effects of the aziridinium ion of ethylcholine (AF64A) have been examined after stereotaxic injection into the rat striatum. In a dose-response study (2-26 nmol), 8 nmol caused a 46% decrease in striatal choline acetyltransferase (CAT) activity with minimal effects on the activities of glutamate decarboxylase (GAD) and tyrosine hydroxylase (TH) at 7 days. Maximal CAT reductions of 78-82% occurred with doses of 16-26 nmol which also caused dose-related decreases in GAD and TH activities that paralleled the progressive decrements in CAT. A time course study with 8 nmol indicated a rapid 20% reduction of CAT activity by 12 h and an additional gradual fall of 20% over the next week; TH and GAD activities were not significantly reduced. The selective inhibition of CAT activity persisted for at least 3 months. Histological examination of Nissl stained sections revealed an area of nonspecific damage at the injection site with an abrupt border surrounded by apparently normal striatal neuropil; however; neuronal perikarya staining intensely for acetylcholinesterase were not reduced. These preliminary findings strongly suggest that AF64A has selective neurotoxic effects against striatal cholinergic neurons while relatively sparing striatal GABAergic intrinsic neurons or dopaminergic afferents.

Relationship between amygdala and hypothalamus in the control of eating behavior

Abstract Continuous, bilateral stimulation of the cortico-medial-pyriform transition zone of the amygdala was shown to suppress food intake in deprived rats. The effect of various bilateral lesions on this phenomenon was tested, each in a different group of animals. Destruction of the ventromedial nucleus of the hypothalamus or severance of the stria terminalis prevented the suppression of eating by amygdaloid stimulation. Lesions in the tail of the caudate nucleus or the dorsal fornix had no effect on suppression of eating. The hypothesis is made that amygdaloid stimulation suppresses food intake by acting via the stria terminalis and the ventromedial nucleus to suppress activity in the lateral hypothalamic area, causing a reduction in food intake.

Induction of mating in male chicks following preoptic implantation of androgen

Abstract Implantation of testosterone propionate in the anterior hypothalamic region of male chicks selectively increased mating behavior of testosterone-primed, low threshold (for mating) subjects. When equivalent subjects were implanted with blank cannulae, or with testosterone propionate in other brain regions, no increase in mating scores occured. The data provide additional evidence for androgen-sensitive mechanisms in anterior hypothalamus and suggest that neural cells mediating mating behavior can be primed or triggered by androgen very early in development.

Comparison of the effects of brain dopamine-depleting lesions upon oral behaviors elicited by tail pinch and electrical brain stimulation ☆

Abstract Rats with extensive brain dopamine (DA) depletions subsequent to 6-hydroxydopamine (6-OHDA) intraventricular injections (2×200 μg) showed relatively normal food-directed responses to tail pinch and to electrical stimulation of the lateral hypothalamus. These eating and gnawing behaviors occurred even in animals that were still spontaneously aphagic after the brain lesion. In contrast, rats with similar brain DA depletions produced by a single intraventricular injection of 250 μg 6-OHDA showed a permanent abolition of electrically-elicited eating, and a chronic reduction in tail pinch behaviors. Rats treated with intranigral 6-OHDA sustained essentially complete striatal and 90% nucleus accumbens DA depletions; they showed a marked absence of both spontaneous and pinch-elicited oral behaviors. We discuss the possible parallels between tail pinch- and electrically-elicited behaviors, their relationship to naturally occurring behavior patterns, and the necessary or sufficient supportive role of nigrostriatal DA.

Effect of atropine on drinking induced by carbachol, angiotensin and isoproterenol.

Abstract Injections into the lateral septal area of either carbachol, angiotensin II, or DL isoproterenol HCl lead to increased drinking in the rat. Preinjections into the septal area of either atropine sulfate or atropine methyl nitrate produce a virtually complete blockade of carbachol induced drinking but have no effect on drinking induced by angiotensin or isoproterenol. Results indicate that angiotensin and isoproterenol induce drinking by a mechanism that may be independent of the cholinergic thirst system. Control data suggest that Angiotensin acts centrally but at non-muscarinic sites to enhance drinking, while isoproterenol probably acts systemically.