The effect of 5-HT2a/2c receptor agonist microinjected into central amygdaloid nucleus and median preoptic area on maternal aggressive behavior in rats

OBJETIVO: Resultados de muitos estudos sustentam a hipótese de que a serotonina (5-HT) está relacionada com a inibição do comportamento agressivo. Foram examinados os efeitos potenciais pró e anti-agressivos do agonista de receptores 5-HT2A/2C em regiões específicas do cérebro. MÉTODO: Ratas fêmeas Wistar no sétimo dia pós-parto receberam microinjeções do agonista seletivo de receptores 5-HT2A/2C, a-methyl-5-hydroxytryptamine maleate (0,2 a 1,0 µg/0,2 µl), no núcleo central da amígdala e núcleo pré-óptico medial. Para cada área estudada, as freqüências dos comportamentos: locomoção, investigação social, postura de ameaça, ataques (frontal e lateral) e ato de morder um intruso, foram comparadas entre os diferentes tratamentos por uma análise da variância, seguida quando apropriado do teste de Tukey. RESULTADOS: Os resultados mostraram que a microinjeção do agonista seletivo a-methyl-5-hydroxytryptamine maleate no núcleo central da amígdala aumentou a agressividade materna, mas não foram encontrados efeitos estatisticamente significativos no comportamento agressivo após a microinjeção do agonista seletivo de receptores 5-HT2A/2C no núcleo pré-óptico medial nas diferentes diluições estudadas. CONCLUSÕES: Os dados atuais e prévios sobre os efeitos pró e anti-agressivos do agonista dos receptores 5-HT2a/2c quando microinjetado no núcleo pré-óptico medial, em comparação com a microinjeção no núcleo central da amígdala, no septo medial (MS) e substância cinzenta periaqueductal em ratas apontam para populações funcionalmente independentes de receptores na amígdala-septo-hipotálamo e substância cinzenta periaqueductal, que são responsáveis pelo controle do comportamento agressivo. É possível que os receptores 5-HT2a/2c da amígdala possam aumentar o comportamento agressivo das fêmeas lactantes, como resultado de mudanças decorrentes do estado emocional de medo.

Gating of the dorsal penile nerve inputs by norepinephrine at the medial preoptic area in rats.

The medial preoptic area neurons related to male sexual behaviour in rats were identified by their responses to dorsal penile nerve stimulation. These neurons were further tested with norepinephrine applied iontophoretically. From the 21 medial preoptic area neurons recorded in urethane anaesthetized rats, 17 neurons responded to dorsal penile nerve stimulation. Excitatory and inhibitory responses were found in almost equal number of neurons. 14 neurons responded to norepinephrine application, out of which six neurons were excited and eight were inhibited. The direction of changes produced by dorsal penile nerve stimulation and norepinephrine application were similar in 10 neurons. The results suggest that the sensory inputs from the genitalia are possibly gated by norepinephrine at the level of the medial preoptic area. Afferent information from the genitalia carried by dorsal penile nerve and the availability of norepinephrine at the level of the medial preoptic area probably help in maintaining adequate level of sexual arousal.

Repeated intracerebral microinjections: efficacy in studying brain functions.

Injection of chemicals into the brain has been considered as an important technique to study various functions of the brain. In these studies, as a rule, only one bilateral injection is given in one animal. This study was undertaken to evaluate the quality of the body temperature data obtained after first and second injections of methoxamine and artificial cerebrospinal fluid into the medial preoptic area. Though there was quantitative decrease in the effects produced after the second injection of the drug, there was no significant change in the effects produced by the second injections of artificial cerebrospinal fluid, which was used as a vehicle. Results of this study support the earlier recommendation to perform only one injection in any of the brain sites for evaluating the effect of any drug. But the vehicle can be administered as a second injection, without compromising on the quality of data.

Why the medial preoptic area is important for sleep regulation.

The medial preoptic area (mPOA) is one of the many areas in the brain that control sleep. Apart from sleep, the mPOA is important for the regulation of body temperature, and other important body functions aimed at energy homeostasis. In sleep regulation, the major function of this area is to maintain sleep. Though the mPOA controls sleep and body temperature through independent neuronal circuits, it is essential for organising the sleep architecture, as per the thermoregulatory requirement. The functional integrity of the mPOA may be essential for the regulation of energy homeostasis, in response to alterations in the ambient temperature, heat producing physical activity and sleep-wakefulness. Thus, the mPOA forms part of the brain that integrates regulations aimed at preservation of self. The mPOA is important for maintaining the "set point" for not only body temperature, but it is also important for maintaining the "set point" for several physiological parameters including sleep-wakefulness.

Asymmetrical effects of the unilateral implant of pilocarpine on the preoptic-anterior hypothalamic area on spontaneous ovulation of the adult rat

The effects on ovulation at the next strus after unilaterally implanting pilocarpine in the preoptic-anterior hypothalamic area (POA-AHA) of rats on each day of the estrous cycle were analyzed. Implantation on the left side of POA-AHA on the day of estrus blocked ovulation in all animals, whereas implantation on the right side did not (0/5 vs. 4/4, p<0.05). Implantation on diestrus 1 or 2 on either side of the POA-AHA blocked ovulation. Implatation on the righ side of the POA-AHA at the day of proestrus blocked ovulation (1/6 animals ovulated), while 10/12 with pilocarpine on the left side ovulated (p<0.05).The administration of 3.7 µg of GnRH at 13:00 h o the expected day of proestrus induced ovulation in 36/42 treated animals. In rat with a pilocarpine implant, the injection of estradiol benoznate on diestrus 2 restored ovulation only in those animals with the pilocarpine implant placed in the left side of the POA-AHA, performed on the day of estrus. The results support the previous estatements that in the adult rat POA-AHA, the cholinergic mechanism regulating preovulatory GnRH release, is lateralized. In addition, at the beginning of the estrous phase, the PAO-AHA-cholinergic system needs to remain undisturbed for normal ovulation to take place at the next estrus

Electrical and chemical stimulation of the same hypothalamic loci in relation to agressive behaviour in cats: a comparison study.

Chemitrodes which permit electrical and chemical stimulation of the same hypothalamic loci were implanted in anterior hypothalamic and preoptic regions. These sites were stimulated electrically using biphasic square wave pulse (1 ms, 60 Hz) at a current strength ranging from 150-800 microA to evoke an aggressive response. At lower current strength of 150-200 micro A, defence response, a sort of non-specific response can be elicited from these regions. Increasing the current strength to 400 microA led to the recruitment of affective and somatic components and changed the response pattern either to affective attack or flight. The loci producing affective attack response were localized more laterally and ventrally while the loci producing flight response were located in the dorsomedial regions of the hypothalamus. In this response the animal made a goal-directed attempt to escape through an escape route. Increasing the current strength to 500 microA in the dorsomedial regions changed the flight response to violent flight, which involved vigorous running with unsheathed claws and attacking objects if obstructed. Similar increase in current strength at loci producing affective attack only led to a decrease in the latency of response and made the attack more vigorous. Microinfusion of carbachol in graded doses of 2-15 microgram at all these loci produced a profound affective display. At lower doses of 2 and 5 microgram, only some components of affective display like alertness, pupillary dilation and ear flatness were exhibited. Increasing the dose to 10 micrograms and 15 micrograms led to the recruitment of other affective components like piloerection, salivation, hissing and baring of teeth. Microinfusion of carbachol at all loci producing affective attack on electrical stimulation produced a prononced affective display while microinfusion of carbachol at loci producing flight response led to the development of defence posture. At six loci a typical flight response was obtained while violent flight was never exhibited at any of these sites. Microinfusion of atropine (10 microgram in 1.0 microliter saline) at these loci completely blocked the carbachol induced response. Both somatomotor and affective components were completely inhibited. However, the responses obtained on electrical stimulation were not totally blocked following atropine infusion and some of the somatomotor and affective components could be elicited with higher current strength. These studies indicate the involvement of cholinoceptive mechanisms in the elicitation of hypothalamically induced aggresive behaviour. Microinfustion of hexamethonium bromide, a nicotinic blocker in 50 micrograms doses did not affect the aggressive response.

Effect of application of gamma amino butyric acid at the medial preoptic area on sleep-wakefulness.

Intracerebral microinjections of gamma amino butyric acid were given bilaterally at the medial preoptic area (mPOA) to determine the possible role of this neurotransmitter in the genesis and regulation of sleep-wakefulness. GABA (50 micrograms/0.2 microliters) when administered through chronically implanted cannulae in free moving rats, did not produce any significant alterations in sleep-wakefulness. This may be attributed either to the non-involvement of GABA at the level of mPOA in the regulation of sleep, or to other factors like the low dose and rapid breakdown of the injected drug.

Effect of carbachol injection in the medial preoptic area on sleep-wakefulness and body temperature in free moving rats.

The aim of the present study was to find out the changes in sleep-wakefulness and body temperature brought about by application of cholinergic agonist, carbachol, in the medial preoptic area (mPOA). Carbachol, when injected bilaterally into the mPOA of male rats, through chronically implanted cannulae, produced a fall in rectal temperature and long lasting arousal. There was temporal dissociation in the duration of changes produced in the two parameters. It is suggested that the cholinergic system at the medial preoptic area brings about arousal response and fall in body temperature through different circuits.

Central angiotensin converting enzyme-blockade and thirst

1. The effect of lisinopril, a potent inhibitor of angiotensin converting enzyme (ACE), injected into the medial preoptic area (MPOA) on water intake was investigated in male Holtzman rats (200-250 g). 2. Injection of lisinopril (2 micrograms/microliters) into the MPOA abolished the water intake induced by subcutaneous (sc) injection of isoprenaline (100 per cent ) and water deprivation (90 per cent ) and drastically reduced the water intake induced by sc injection of polyethyleneglycol (60 per cent ). A small reduction of water intake induced by lisinopril was also observed 90 and 120 min after sc hypertonic saline (N = 10 for each group). 3. These results suggest that central ACE activation, particularly in the MPOA, plays an important role in the dipsogenic responses induced by the agents studied

Responses of pre-optic area to intracerebroventricular thyroxine and thyrotropin in dog brain.

Electroencephalographic activity (EEG) of pre-optic area (POA) was recorded after intracerebroventricular (ICV) microinjection of thyroxine (T4) and thyrotropin (TSH) in conscious male dogs. Recordings were made for two hours following microinjections. Biphasic responses with increased amplitude were observed in both the treatments, but chronologically the responses obtained with T4 & TSH were opposite to each other.

Thermal changes produced by norepinephrine application in the preoptic area of monkeys.

The effect of injection of norepinephrine in the anterior regions of hypothalamus on rectal temperature, skin temperature, heart rate and respiratory rate in rhesus monkeys was studied. The injection of 2 micrograms of norepinephrine in the preoptic area produced a fall in body temperature without any accompanying change in skin temperature, heart rate and respiratory rate. The findings suggest that the suppression of heat production may be responsible for the norepinephrine induced hypothermia in monkeys.

Effect of atropine injection into the medial septal area on food-associated drinking

The effect of atropine injection into the medial septal area (MSA) or medial preoptic area (MPOA) on carbachol-induced drinking was evaluated in conscious unrestrained rats during a food-associated drinking test reinforced by 14 h of food deprivation. Atropine did not alter food intake when injected into either area, nor did it affect drinking after its injection into the MPOA. However, atropine markedly reduced water intake after its injection into the MSA. These results suggest that the central cholinergic system in the MSA can participate in the regulation of food-associated drinking

Effects of succinylcholine and related substances administered into the medial preoptic area on the local EEG, body temperature, heart rate, galvanic skin resistance and biogenic amines.

Succinylcholine (Sch) which is a cholinergic neuromuscular blocker has been known to occasionally lead to episodes of malignant hyperthermia in swine and humans. In order to find whether it produces any hyperthermic effects through action on medial preoptic area, experiments were carried on by administering intracerebrally the chemical into the medial preoptic area through an in-dwelling cannula-cum-electrode in the free moving rat. The changes in body temperature and the local EEG were studied. For comparison purpose, the effects of carbachol, atropine and phenylephrine were also studied. Further, in the curarized state of no muscular activity, the effect of SCh on the preoptic area was again tested and also the changes in the other autonomic parameters of heart rate and galvanic skin resistance (GSR) were studied. It was observed that SCh given into preoptic area caused a clear hyperthermic effect. The effect was countered by prior administration of atropine into the site. After SCh the local EEG changed into a high amplitude slow wave format. The heart rate was not altered but the GSR increased by two-fold. Carbachol caused a rise in body temperature, heart rate and also GSR. SCh also caused a reduction in noradrenaline content of the hypothalamus by 23% while no change in dopamine and serotonin occurred. Serotonin increased by 28% in the brainstem with no change in the other amines. Septum showed an increase of noradrenaline and dopamine contents by 40% and 25% respectively. Keeping in view the monoaminergic connections and thermoregulatory role of the preoptic area, one may postulate that SCh could inhibit the warm sensors and the controls of the dual sympathetic mechanism which normally leads to an increase of sudomotor activity and a decrease of vasomotor activity, the inhibition resulting in rise of body temperature.