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The short-term effects of testosterone on brain protein synthesis in 4-day-old rats: an electrophoretic study of proteins following intraventricular injection of [35S]methionine.

The short-term effects of administering testosterone propionate (TP) to 4-day female rats (androgenized females) on the synthesis of specific brain proteins were investigated. At various times after the intraperitoneal injection of TP or arachis oil, [35S]methionine was injected into the third ventricle and 1 h later proteins were extracted from the hypothalamus-preoptic area (H-POA) and analyzed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Changes in synthesis of two 13,000-14,000 mol. wt. proteins in the 4-day rat brain were detected, and these changes appeared to be specific for the H-POA. In addition, silver staining revealed a 50,000 mol. wt. protein which was present in the male and androgenized female H-POA but not in the oil-treated female H-POA. An incidental, but potentially important finding, was the synthesis of a 77,600 mol. wt. protein in the H-POA of one animal which had several seizures during the experiment. These results show that changes in the synthesis of specific proteins occur in the H-POA of neonatal female rats within 8 h of TP administration and support the hypothesis that hormone-induced changes in brain protein synthesis may be involved in sexual differentiation of the brain.

Animals↗

Intraventricular injection of antiserum to nerve growth factor delays the development of amygdaloid kindling.

To investigate the possibility that nerve growth factor (NGF) may play some role in the development of kindling, rabbit anti-NGF serum was injected into the third ventricle on the first 3 days of daily electrical stimulation of the basolateral amygdala. The number of stimulations required to reach full amygdaloid kindling increased significantly in the rat injected with anti-NGF serum compared to that in the rat injected with normal rabbit serum. It was confirmed that anti-NGF serum did not act as an anticonvulsant. The results demonstrate that NGF may be important for the long-lasting neuronal changes induced by daily electrical stimulation of the amygdala.

Amygdala↗

Intraventricular injection of vasoactive intestinal polypeptide facilitates the development of amygdaloid kindling.

To determine the involvement of vasoactive intestinal polypeptide (VIP) in the development of kindling in rats, VIP or antibody to VIP (anti-VIP) was injected into the third ventricle after the daily stimulation of the basolateral amygdala. The number of stimulations required to reach full amygdaloid kindling was significantly smaller in rats treated with VIP than rats treated with saline, whereas it increased significantly in rats treated with anti-VIP compared to that in the rats treated with either saline or normal rabbit serum. The results suggest that VIP participates in the development of amygdaloid kindling as a facilitatory factor.

Amygdala↗

Prevention and reversal of tolerance to barbiturates by intraventricular injection of hemicholinium-3.

Intracerebroventricular (i.c.v.) injection of phenobarbital, 800 mug, or intraperitoneal (i.p.) injection of hexobarbital, 100 mg/kg, into rats resulted in a loss of righting reflex lasting 15.4 +/- 0.2 min and 20.7 +/- 0.7 min, respectively. A 40-60% reduction in this response was obtained following administration of phenobarbital either i.c.v. (800 mug 4 times daily) or i.p. (80 mg/kg/day) for 4 days. Although these treatments also increased hepatic mixed function oxidase activity, this enzyme induction was shown to be unrelated to the development of tolerance to loss of righting reflex. I.c.v. injection of hemicholinium-3 (HC-3) in doses which reduce brain acetylcholine levels (4-20 mug) profoundly affected tolerance to the central depressant effect of the barbiturates. Thus, depending upon the time of administration, HC-3 either retarded or prevented development of this tolerance. Moreover, if tolerance was allowed to progress normally, administration of HC-3 on day 4 or 5 returned the duration of the loss of righting reflex toward normal values. HC-3 did not influence either the duration of this response in non-tolerant rats or the induction of the hepatic mixed function oxidase activity. These results suggest that brain ACh plays an important role in the development and maintenance of tolerance to the central depressant effects of barbiturates.

Animals↗

Thermoregulatory effects of intraventricularly injected dopamine in the goat.

Dopamine (DA) was injected in the third brain ventricle of goats and the thermoregulatory effects were studied under different ambient conditions. The effects depended on dose, ambient conditions and cannula used. In the cold, there was a drop in body temperature, sometimes accompanied by suppression of shivering and by vasodilatation. Both temperature decrease and suppression of shivering were dose-dependent but there was no relation between magnitude of temperature drop and occurrence of shivering suppression. In a thermoneutral environment, there was either a slight vasoconstriction or hypothermia, occasionally accompanied by induction of panting. In the heat, either hypothermia or hyperthermia was observed. Hypothermia was accompanied by an increase in panting. Hyperthermia only occurred when the animals became excited as a result of the injection of DA. It is concluded that DA acts by stimulating the thermoregulatory pathway from heat sensors to heat loss effectors at a locus similar to that for 5-hydroxytryptamine in the thermoregulation model of Bligh et al. (1971).

Animals↗

Suppression of operant responding for food and water reinforcement following intraventricular injections of Bombesin in the rat.

The effects of injecting Bombesin (BBS) into the lateral cerebral ventricle on operant responding for food and water in the rat were investigated in two experiments. In the first experiment injections of BBS suppressed both operant responding for water and post-session water consumption. A combined treatment of water preloading and BBS injections produced greater suppression of post-session water consumption than either BBS injections or water preloading. This suggests that the peptide has a primary antidipsic effect. In the second experiment BBS produced a significant suppression of operant responding for food reward as well as lowered body temperature. This suggests that BBS may serve as a true satiety signal for food motivated behavior.

Animals↗

Intraventricular injection of an N-methyl-D-aspartate antagonist disrupts vestibular compensation.

Guinea pigs which had compensated for a unilateral labyrinthectomy exhibited a loss of ocular motor and postural compensation when a 40 or 20 mM concentration of the NMDA antagonist CPP, was injected through a cannula implanted in the IVth ventricle close to the vestibular nuclei. Similar injections of artificial cerebrospinal fluid did not induce loss of compensation. These results suggest that NMDA receptors may contribute to vestibular compensation in the guinea pig.

Animals↗

Induction of mouse-killing in the rat by intraventricular injection of a GABA-agonist.

Intracerebroventricular injections of THIP (2.5 and 5.0 micrograms in 5 microliter) facilitated elicitation of mouse-killing in killer rats placed in a non-familiar environment. The same doses induced well organized mouse-killing responses in 60% of non-killer rats. Concomitantly food intake was elicited. Exploratory activity as well as orientation and approach towards any sensory stimulus were also increased. On the contrary, intracerebroventricular injections of bicuculline methiodide (65 and 125 ng in 5 microliters) suppressed aggressive responses in killer rats. The data support the view that GABA receptors are involved in mechanisms which facilitate elicitation of mouse-killing behaviour as well as other positively motivated responses.

Aggression↗

Elicitation of conspecific attack or defense in the male rat by intraventricular injection of a GABA agonist or antagonist.

The involvement of central GABAergic mechanisms in the control over offensive and defensive behaviours in the rat was studied using intracerebroventricular injections (5 microliter) of a GABA agonist (THIP) or a GABA antagonist (bicuculline methiodide). Intracerebroventricular injections of THIP (1.25 and 2.5 micrograms) induced attacks and offensive sideways towards an untreated partner, in animals placed in a neutral area where no aggressive reactions occur in controls. Social approach behaviours (partner investigation, allogrooming) were also increased in both attacking and non-attacking animals, whereas individual behaviours (cage exploration, autogrooming, immobile posture) were decreased. Inversely, intracerebroventricular injections of bicuculline methiodide (62.5 and 125 ng) suppressed offensive items (attacks, offensive sideways, upright postures) in resident animals confronted with untreated intruders and increased occurrence of defensive sideways. This treatment also decreased reactions oriented towards the partner (investigation, allogrooming and crawl under/over), while increasing individual behaviours (cage exploration, immobile posture). These data demonstrate that activation of central GABA receptors elicits intraspecific offensive behaviours in the rat. On the contrary, blockage of these receptors induces defensive reactions and suppresses offensive behaviours. The involvement of these receptors in the neural control over aggressive behaviour in the rat is discussed.

Aggression↗