Effects of intra-amygdaloid TRH injections on motor activity and dominant-submissive behavior in rats competing for water.

The effect of thyrotropin releasing hormone (TRH) microinjections into the central amygdala (10 g in 0.5 1 into each side) on locomotor activity water intake and dominance behavior in a water competition test was investigated in male Wistar rats. TRH increased the general motility without altering the number of rearings. Intra-amygdaloid TRH injection to submissive rats resulted in a loss of subordinate position in these animals in the water competition test. A tendency to decrease dominance followed the injection of the peptide to the dominant animals. The effect of TRH in the dominance test does not appear to involve influence on the thirst drive as microinjection of the peptide did not change significantly the water consumption in thirsty rats.

On the relative importance of D-1 vs. D-2 dopaminergic receptors in the control of audiogenic seizures in ethanol withdrawn rats.

Bromocriptine, a mixed D-1/D-2 dopaminergic receptor agonist and SKF 38393, a D-1 specific agonist were found to alleviate the incidence and intensity of audiogenic convulsions in ethanol withdrawn rats. (+) and (-)3-PPP, putative D-2 autoreceptor agonists, were without effect in the test. SCH 23390, a D-1 specific antagonist did not influence seizure intensity in ethanol withdrawn or ethanol naive animals. It is suggested that D-1 receptors may play a role in convulsive response during ethanol withdrawal.

Different effect of diltiazem and nifedipine on some central actions of ethanol in the rat.

The effect of two Ca2+ channel inhibitors (CCIs) on ethanol-induced hypothermia and hypnosis, on tolerance formation to both effects, and on audiogenic convulsions during ethanol withdrawal was studied in rats. Nifedipine, 2 and 5 mg/kg IP, significantly augmented the hypnotic action of ethanol without affecting hypothermia. Diltiazem failed to influence either effect of the toxin. Rectal temperature did not change in ethanol-naive rats after acute injection of diltiazem or nifedipine. Both drugs dose-dependently suppressed the development of tolerance to the hypothermic effect of ethanol without affecting the tolerance to the hypnotic action. Only nifedipine markedly suppressed the audiogenic seizure response in ethanol withdrawn animals. These data suggest that Ca2+ channels play a role in both acute and chronic effects of ethanol while pointing to certain differences in behavioral effects of various CCIs.

Inhibition of affective aggression and dominance in rats after thyrotropin-releasing hormone (TRH) microinjection into the nucleus accumbens.

The effect of 10 micrograms TRH injected bilaterally into the nucleus accumbens septi on two models of affective aggression and on dominance in a water-competition task was investigated in pairs of male Wistar rats. TRH significantly suppressed affective shock-induced and apomorphine-induced fighting. It also decreased dominance when administered to dominant rats while no effect was noted upon injection into subordinate animals. The peptide influenced neither water consumption in thirsty rats nor the pain threshold in a hot plate test.

Inhibition of p-chlorophenylalanine-induced muricide behavior following TRH microinjection into the limbic structures in the rat.

The effect of central microinjections of thyrotropin releasing hormone (TRH) on muricide behavior was investigated in rats with chronically implanted cannulas into one of the limbic structures: the amygdala, the hippocampus or the nucleus accumbens. The rats were made aggressive by p-chlorophenylalanine administration. Saline injection did not inhibit muricide, whereas TRH (10 micrograms in 0.5 microliter per side) significantly suppressed mouse-killing reaction upon injection into each of three regions. It is suggested that the observed antiaggressive effect of TRH may involve stimulation of the central noradrenergic and/or serotonergic transmission.

Differential effects of chronic ethanol on apomorphine-induced locomotion, climbing and aggression in rats.

Male Wistar rats were tested for apomorphine-induced locomotion, climbing and aggression after 3 week's intragastric ethanol (EtOH) treatment, 5 g/kg as 20% solution daily. The ability of apomorphine (APO) to elicit rearing (1 mg/kg i.p.) and climbing (0.5 mg/kg i.p.) was significantly suppressed in EtOH withdrawn animals. General locomotor activity in response to 1 mg/kg of APO i.p. did not differ between control and EtOH-treated groups. Affective aggression was checked in pairs of low-aggressive rats, i.e. resistant to the aggression inducing action of 10 mg/kg APO. No symptoms of aggression appeared in control animals whereas EtOH administered rats responded with marked aggression to APO. The different effect of chronic EtOH on responsiveness to APO in three behavioral models is discussed in terms of varying involvement of dopaminergic systems and receptors in behavioral phenomena as well as their susceptibility to prolonged EtOH.

Norepinephrine-mediated suppression of apomorphine-induced aggression and locomotor activity in the rat amygdala.

The effect of injections of norepinephrine (NE)-depleting toxin DSP-4 into the central amygdala (AMY) on apomorphine-induced fighting (AIF) was studied. In addition, the influence of such treatment on related parameters such as spontaneous activity, pain sensitivity and changes in locomotion after (+)3-PPP or apomorphine (1 mg/kg SC each) were verified. Finally, injections of NE or phenylephrine into the AMY five min before AIF were performed. DSP-4 induced marked (-71%) and selective fall in NE within the AMY accompanied by significant increase in aggressive response to 5 mg/kg of apomorphine. DSP-4-treated animals were less active in the open field and more sensitive to pain in a hot plate test. They were also more responsive to locomotor-augmenting action of apomorphine. Significant suppression of AIF was seen after injections of NE and phenylephrine into the AMY. The results suggest that NE input to the AMY plays an inhibitory role in dopamine-related locomotion and aggressivity. Moreover, amygdalar NE appears to be involved in general activity and pain perception modulation.

Suppression of ethanol tolerance and dependence in rats treated with DSP-4, a noradrenergic neurotoxin.

The formation of tolerance to the hypothermic effect of ethanol was inhibited in rats after intraperitoneal injection of the neurotoxin DSP-4 50 mg/kg. The neurotoxin also significantly suppressed the ethanol withdrawal syndrome; hyperlocomotion, audiogenic seizures and spasticity. These behavioural changes were accompanied by a 52% decrease of the brain norepinephrine (NE) content, with no alterations in the dopamine or serotonin levels. The results indicate that intact NE neurons are necessary for the development of tolerance to ethanol-induced hypothermia and are involved in the expression of the ethanol withdrawal syndrome.

The effect of oxytocin and fragment (MIF-I) on the development of tolerance to hypothermic and hypnotic action of ethanol in the rat.

The daily pretreatment of rats with oxytocin (OXY) or MIF-I prior to ethanol (Et-OH) administration markedly altered the alcohol tolerance when tested on the fifth day of treatment. OXY (800 and 2400 nmole/kg SC) and MIF (800 nmole/kg SC) inhibited the development of tolerance to the hypnotic effect of Et-OH. MIF at this dose also inhibited the tolerance to the hypothermic effect. Only OXY in the dose of 800 nmole/kg suppressed hypothermia in an acute experiment with Et-OH and produced by itself hypothermia after acute administration (2400 nmole/kg). The tolerance to this last effect developed after four days of peptide treatment. The results indicate that OXY and MIF-I can influence the processes of development of tolerance to some central depressive effects of Et-OH in rats.

Further studies on the role of noradrenergic mechanisms in ethanol withdrawal syndrome in rats.

Ethanol dependence was induced in rats by intragastric administration of ethanol. Clonidine (0.1 mg/kg ip) suppressed withdrawal reaction while yohimbine (2.5 mg/kg ip) produced an opposite effect. Propranolol (2.0 mg/kg ip) reduced withdrawal convulsions but not locomotor hyperactivity while prazosin (1.0 mg/kg ip) attenuated only the latter symptom. Electrolytic lesions in the ventral noradrenergic bundle slightly increased locomotor activity in ethanol-dependent rats but failed to change the convulsions. Our result indicates that drugs acting upon alpha and beta adrenoceptors are able to reduce the severity of certain withdrawal reactions in ethanol-dependent rats.

Effects of 6-hydroxydopamine-induced lesions of A10 dopaminergic neurons and neuroleptic or bromocriptine treatment on ethanol withdrawal syndrome in rats.

In this study we have investigated the possible role played by dopaminergic mesocorticolimbic neurons in ethanol withdrawal syndrome in rats. 6-hydroxydopamine-induced bilateral lesions of A10 nucleus resulted in selective fall in forebrain dopamine content accompanied by enhanced motor activity and audiogenic seizure intensity when measured during withdrawal period. Opposite changes, hypolocomotion and lower seizures intensity, were observed after metoclopramide injection. Pimozide also diminished seizure intensity but at higher dose (0.4 mg/kg) produced an increase in locomotor activity. Bromocriptine, an agonist of dopaminergic receptors, depressed both locomotor activity and audiogenic seizure intensity. It is concluded that mesolimbic dopaminergic neurons may be involved in the mechanism of ethanol withdrawal syndrome.

Some behavioral effects of chlorodesmethyldiazepam and lorazepam.

Two benzodiazepine derivatives, chlorodesmethyldiazepam (CDD) and lorazepam (LOR) were compared in rats and mice in some behavioral tests. Both compounds similarly depressed audiogenic seizures, facilitated the behavior suppressed by punishment (conflict test) and produced muscle relaxant and sedative effects as measured in a rota-rod test. In low and moderate doses CDD paradoxically increased shock-induced fighting while in a higher dose it strongly reduced this behavioral pattern.

Effects of lesion of the locus coeruleus and clonidine treatment on ethanol withdrawal syndrome in rats.

Ethanol dependence was induced i Wistar male rats by administration of ethanol by gavage for 5 days in 3 fractional doses. Clonidine (0.1 mg/kg ip) strongly reduced the withdrawal syndrome. Bilateral lesions in the nucleus locus coeruleus were also able to decrease several withdrawal signs. Our data indicate that drugs decreasing activity of noradrenergic brain neurons might be useful in treatment of ethanol dependence.