Lesions of the paraventricular thalamic nucleus attenuates prepulse inhibition of the acoustic startle reflex.

The paraventricular thalamic nucleus (PVT) is a midline nucleus with strong connections to cortical and subcortical brain regions such as the prefrontal cortex, amygdala, nucleus accumbens and hippocampus and receives strong projections from brain stem nuclei. Prepulse inhibition (PPI) is mediated and modulated by complex cortical and subcortical networks that are yet to be fully identified in detail. Here, we suggest that the PVT may be an important brain region for the modulation of PPI. In our study, the paraventricular thalamic nuclei of rats were electrolytically lesioned. Two weeks after the surgery, the PPI responses of the animals were monitored and recorded using measurements of acoustic startle reflex. Our results show that disruption of the PVT dramatically attenuated PPI at prepulse intensities of 74, 78 and 86dB compared to that in the sham lesion group. Thus, we suggest that the PVT may be an important part of the PPI network in the rat brain.

Investigation of the role of alpha-2 adrenergic receptors on prepulse inhibition of acoustic startle reflex in rats.

OBJECTIVES: Alpha-2 adrenergic receptors target several behavioral functions. These receptors may connect with the brain pathways mediating sensorimotor gating system that associate with psychoses, and the literature that investigate the relationship between alpha-2 receptors and sensorimotor gating system is very limited and some results are controversial. Thus, we aimed to investigate the role of alpha-2 receptors on prepulse inhibition (PPI) of acoustic startle reflex which is a measure of sensorimotor gating. EXPERIMENTAL DESIGN: Adult male Wistar rats were subjects. PPI was measured as the per cent inhibition of the startle reflex produced by a startling pulse stimulus. The average PPI levels were used in the further analyses. Clonidine (0.03-1 mg/kg), an agonist of alpha-2 receptors, idazoxan (10 mg/kg), an antagonist alpha-2 receptors, and saline were injected to rats intraperitoneally. PPI was evaluated at two different startle intensity levels (78 and 86 dB, respectively). PRINCIPAL OBSERVATIONS: Treatments produced some significant changes on PPI of startle reflex at all two levels of startle intensity. While clonidine (0.06, 0.25, 0.5, and 1 mg/kg) disrupted significantly PPI, idazoxan (10 mg/kg) did not produce any significant effect on PPI. However, pretreatment with idazoxan reversed significantly clonidine-induced disruption of PPI. Neither idazoxan (10 mg/kg) nor clonidine (1 mg/kg) produces any significant change on locomotor activity in naive rats. CONCLUSION: Because idazoxan and clonidine also act through imidazoline receptors, our results suggest that alpha-2 and/or imidazoline receptors are associated with PPI of acoustic startle reflex in rats. Stimulation of these receptors may cause sensorimotor gating disturbances.

Locomotor stimulation by acute propofol administration in rats: Role of the nitrergic system.

BACKGROUND: The addictive potential of propofol has been scientifically discussed. Drugs' psychostimulant properties that can be assessed via measurements of locomotor activity are linked to their addictive properties. No studies that have investigated the effects of propofol on locomotor activity have been reported to date. The present study sought to investigate the effects and possible mechanisms of action of propofol on locomotor activity in rats. METHODS: Adult male albino Wistar rats (250-330g) were used as subjects. The locomotor activities of the rats were recorded for 30min immediately following intraperitoneal administration of propofol (20 and 40mg/kg), saline or vehicle (n=8 for each group). NG-nitro arginine methyl ester (l-NAME, 15-60mg/kg), a nitric oxide (NO) synthase inhibitor, and haloperidol (0.125-5mg/kg), a non-specific dopamine receptor antagonist, were also administered to other groups of rats 30min prior to the propofol (40mg/kg) injections, and locomotor activity was recorded for 30min immediately after propofol administration (n=8 for each group). RESULTS: Propofol produced significant increases in the locomotor activities of the rats in the first 5min of the observation period [F(2,21)=9.052; p<0.001]. l-NAME [F(4,35)=3.112; p=0.02] but not haloperidol [F(4,35)=2.440; p=0.067] pretreatment blocked the propofol-induced locomotor hyperactivity. l-NAME did not cause any significant change in locomotor activity in naïve rats [F(2,21)=0.569; p=0.57]. CONCLUSIONS: Our results suggest that propofol might cause a short-term induction of locomotor activity in rats and that this effect might be related to nitrergic but not dopaminergic mechanisms.