Endocrine and behavioral traits in low-avoidance Sprague-Dawley rats.

In the present series of experiments, we have examined the endocrine profile of two stable colonies of Sprague-Dawley rats, here labeled Stock A, and Stock B, differing markedly in their ability to acquire a conditioned avoidance response. On separate occasions, the animals were subjected to five daily sessions (approximately 20 trials per 15 min session) of conditioned avoidance training, measurements of startle reactivity to an auditory stimulation and open-field spontaneous locomotor activity observations. The experiments were concluded by taking blood samples for later analysis of plasma glucose and plasma levels of the following hormones: insulin, gastrin, CCK, glucagon, somatostatin, oxytocin and corticosterone. The low-performing Stock B animals were characterized by [1] being more reactive to sensory stimulation: higher startle amplitude and shorter startle latency; [2] having higher plasma insulin and corticosterone levels, whereas plasma gastrin and oxytocin were significantly lowered and a strong tendency for a decrease also in plasma CCK. There were no differences in spontaneous locomotor activity between the two substrains. Taking total variability in avoidance performance into account, there was a statistically significant positive correlation between plasma oxytocin, as well as gastrin, levels and avoidance performance. The evidence obtained here, and in other laboratories, suggests that the Stock B animals display hormonal changes indicative of a submissive-defensive reaction pattern. Thus, the avoidance acquisition deficits displayed by the present Sprague-Dawley stocks A and B, are in all probability caused by emotional reactions when challenged with external stimuli requiring active responding.

Effects of lisuride and quinpirole on convulsions induced by hyperbaric oxygen in the mouse.

Two ergot derivatives, lisuride and quinpirole, were examined for their ability to antagonize hyperbaric oxygen-induced (5 ATA O2) convulsions in mice. Significant protection was obtained by lisuride (25-400 micrograms.kg-1, i.p.) and quinpirole (100-200 micrograms.kg-1, i.p.). The efficacy was found to be about 50% of the protection obtained by diazepam (4 mg.kg-1, i.p.). Both lisuride and quinpirole significantly reduced rectal temperature at all doses administered. In separate experiments, at normal atmospheric conditions, all drugs to some extent reduced estimated respiratory minute volume. Taking these effects into account, lisuride is considerably more active as an anticonvulsant than quinpirole.

Partial protection against hyperbaric oxygen induced convulsions by dopaminergic agents in mice: possible involvement of autoreceptors?

In the present report we have investigated the effects of apomorphine, (-)3-PPP, L-DOPA and haloperidol on the elicitation of convulsions induced in mice by exposure to oxygen at high pressure (HBO) (5 ata O2). It was found that the administration of apomorphine (0.025-0.1 mg X kg-1 s.c.), (-)3-PPP (4 mg X kg-1 i.p.) L-DOPA (200-400 mg X kg-1 i.p.) as well as haloperidol (0.25-2.0 mg X kg-1 i.p.) produced a significant protection against HBO-induced convulsions. Haloperidol was the only drug to produce a dose-dependent decrease in respiration, and this effect does probably explain the anticonvulsant effects observed. The low doses at which apomorphine was effective, and the effects produced by (-)3-PPP, indicate an effect mediated via DA autoreceptors. Alternatively, and more likely taking the effects of L-DOPA into account, the DA receptors involved are sensitive enough to disclose postsynaptic agonist properties of apomorphine and (-)3-PPP at the doses employed.

Central 5-HT and the respiratory response to acoustic stimulation in awake rats: effects of PCPA, 5-HTP and 8-OH-DPAT.

It was found that PCPA (4 X 50-100 mg/kg) decreased the respiratory response to tone pulses (acoustic reaction), and this effect was antagonized by the administration of 5-HTP (25 mg/kg), after inhibition of extracerebral aromatic amino acid decarboxylase by means of benserazide (25 mg/kg). A further increase in the dose of 5-HTP, 50-100 mg/kg, in animals not treated with PCPA did not significantly affect the acoustic reaction. The putative 5-HT agonist 8-OH-DPAT produced a decrease in the acoustic reaction (but also at higher doses some desynchronization of respiration with tone). The administration of d-amphetamine, 0.5-2.0 mg/kg, resulted in an increase in the acoustic reaction. Thus, in the present experiment, using a simple sensory-motor response, 8-OH-DPAT behaves as a 5-HT antagonist and the results provide further support for mixed 5-HT receptor agonist/antagonist properties of this compound.

Enhancement by the putative 5-HT receptor agonist 8-OH-2-(di-n-propylamino)tetralin of the acoustic startle response in the rat.

Two 2-(di-n-propylamino)tetralin (DPAT) compounds, 8-OH-DPAT and 5-OH-DPAT, with reported effects on central 5-HT and DA receptors respectively, were tested for their effects on the acoustic startle response in rats. 8-OH-DPAT was given in doses of 0.25-2.0 mg/kg IP and 5-OH-DPAT in doses of 1.0-8.0 mg/kg IP. Both compounds increased the startle response significantly in a dose-dependent manner, but 8-OH-DPAT appeared to be about 30 times as potent and to have a higher efficacy than 5-OH-DPAT. In addition, the effects on the startle response of L-5-HTP, 25-100 mg/kg IP, and L-dopa, 25-100 mg/kg IP, administration to animals pretreated with the inhibitor of aromatic L-amino acid decarboxylase, benserazide (25 mg/kg IP) were included for comparison. A small, but significant increase in the startle amplitude was found after the highest dose of L-5-HTP, whereas no effects were observed after L-dopa administration.

Enhanced suppression of a conditioned avoidance response by haloperidol but not phenoxybenzamine in rats with bilateral parafascicular lesions.

Male rats were subject to bilateral lesions in the parafascicular nucleus (PF) of the thalamus. The lesions had little or no effect on the performance of a pre-operatively acquired conditioned avoidance response. However, the PF lesioned animals displayed an enhanced response to the dopamine receptor blocking agents haloperidol or pimozide but not to the noradrenaline receptor blocking agent phenoxybenzamine. The results indicate that intralaminar thalamic nuclei and dopaminergic extrapyramidal motor pathways are functionally connected.