Prepulse inhibition following lesions of the inferior colliculus: prepulse intensity functions.

The magnitude of the acoustic startle response can be reduced by a relatively weak sound presented immediately before the startle-eliciting sound; this phenomenon has been termed prepulse inhibition (PPI). Previous studies reported that PPI was present in the decerebrate rat, indicating that the primary neural pathways mediating PPI are located in the brainstem. The present study investigated the effects of focal excitotoxic lesions of the inferior colliculus (IC) on acoustic PPI in rats. In the first part, startle magnitudes were measured in six normal rats as the interstimulus interval (ISI) between the prepulse and startle-eliciting sounds varied between 10 and 100 ms. Prepulse-inhibited startle changed in an ISI-dependent manner with the most effective ISI at 50 ms. In the second part, 21 rats were assigned to three groups: normal unoperated, cortical lesion, and IC lesion. With the ISI fixed at 50 ms, as the prepulse sound level increased from 29 to 49 dB SPL, startle responses decreased quickly in both normal and cortical lesion rats. However, rats with unilateral IC lesions made with ibotenic acid had significantly lower PPI but did not display any increase in startle magnitude. These data suggest that the IC is an important structure in the neural circuit mediating acoustic PPI.

Differential action of NMDA antagonists on cholinergic neurotoxicity produced by N-methyl-D-aspartate and quinolinic acid.

1. Injections of N-methyl-D-aspartate (NMDA) and quinolinic acid (Quin), agonists that activate NMDA receptors, into the rat nucleus basalis magnocellularis (nbM) produced a dose-related decrease in cholineacetyltransferase (ChAT) activity in the cerebral cortex and amygdala 7 days after injection. 2. In order to examine the possibility that NMDA and Quin activate different sub-types of NMDA receptors to produce central cholinergic neurotoxicity, the sensitivity of these agonists to the action of three different NMDA receptor antagonists, 2-amino-7-phosphonoheptanoate (AP-7), 7-chlorokynurenate and dizolcipine (MK801) was examined by injecting a fixed dose of NMDA (60 nmol) or Quin (120 nmol) in combination with different doses of the antagonists into the nbM. 3. Both AP-7 (0.6-15 nmol) and 7-chlorokynurenate (3.75-200 nmol), which block the NMDA receptor recognition site and glycine modulatory site respectively, produced a dose-related attenuation of the NMDA or Quin-induced decrease in ChAT activity in both the cortex and amygdala. Both antagonists showed a greater potency against the action of NMDA than against Quin. 4. MK801 (2-200 nmol), an NMDA receptor-linked channel blocker, attenuated the Quin and NMDA response only at a high dose. Unlike AP-7 and 7-chlorokynurenate, MK801 did not exhibit a consistent difference in its potency as an antagonist against NMDA and Quin. 5. The differential antagonist actions of AP-7 or 7-chlorokynurenate against NMDA and Quin-induced cholinergic neurotoxicity suggest that the excitotoxic actions of these two agonists are mediated via distinct NMDA receptor sub-types. The NMDA- and Quin-sensitive receptors appear to differ with respect to properties of the receptor recognition and glycine modulatory sites that are associated with these receptors.

Neuropeptide Y and behaviour: effects of intrastriatal NPY on circling behaviour of rats.

Neuropeptide Y (NPY) is a member of the pancreatic polypeptide family and consists of 36 amino acids, sharing sequence homologies with the putative gut hormone peptides YY and PP. NPY dose-dependently stimulates food intake when administered icv into the paraventricular hypothalamic nucleus of rats. Icv NPY has also been reported to decrease locomotor activity, rearing and grooming behaviour. Little behavioural research focusing on other unconditioned behaviours has been conducted. However, intrastriatal injections of NPY have been shown to increase dopamine (DA) turnover there. As unilateral manipulations of central DA result in turning away from the side of higher DA activity, it is of interest to evaluate the effects of intrastriatal NPY on this behaviour. Preliminary results indicate that NPY produces a significant contralateral turning bias when injected directly into the striatum. This raises the intriguing possibility that contralateral turning induced by intrastriatal NPY may be mediated by DA.

Circling behavior following unilateral microinjections of cocaine into the medial prefrontal cortex: dopaminergic or local anesthetic effect?

Dopaminergic projections to the medial prefrontal cortex have been implicated in cocaine reinforcement; therefore, it was of interest to examine the locomotor effects of acute administration of cocaine to this area. Circling behavior was assessed following injections of 1.0 microliter of cocaine in doses of 0 (0.9% saline), 25, 50, and 100 micrograms/microliters into the medial prefrontal cortex of rats prepared with chronic unilateral guide cannulae. Animals were scored during four 5 min intervals of a 60 min test session that began with the central injection and placement in a flat circular arena. Cocaine was found to produce dose-dependent contraversive circling, an effect previously seen with the dopamine (DA) agonists LY 14 1865 and (+)-amphetamine, suggesting a unilateral stimulant effect. However, since cocaine has potent local anesthetic properties that have been reported to produce behavioral effects and also to inhibit the reuptake of norepinephrine and 5-HT, it was important to demonstrate that the directional bias was a dopaminergic effect. Intra-frontocortical microinjections of the local anesthetic procaine (10, 100, and 1000 micrograms in 0.5 microliter) did not induce circling. Sulpiride (0.001-10.0 micrograms in 0.5 microliter), a DA antagonist specific for the D-2 receptors, produced ipsiversive circling in a dose-dependent manner in rats treated with (+)-amphetamine (1.5 mg/kg, i.p.). In addition, sulpiride (1.0 micrograms in 0.5 microliter) blocked the circling behavior induced by cocaine (50 micrograms in 0.5 microliter) when administered into the medial prefrontal cortex 15 min prior to the cocaine injection. These results provide further evidence for an excitatory influence of mesocortical DA on motor control.

Functional activity in the lateral habenular and dorsal raphe nuclei following administration of several dopamine receptor antagonists.

2-[14C]deoxyglucose autoradiography was used to show regional functional activity in the rat brain following administration of the dopamine antagonists, cis-flupenthixol, metoclopramide, and pimozide. Elevation of functional activity was observed in the lateral habenula (LHb) following administration of all antagonists. The dorsal raphe nucleus (DR) exhibited decreased functional activity following cis-flupenthixol, which exerts effects at both the D1 and D2 receptors, but not following pimozide or metoclopramide, which primarily act at the D2 receptor. These results converge with previous reports suggesting that the functional status of the LHb is regulated by dopaminergic systems, and that LHb efferents may exert a major influence upon DR neurons. These data further suggest that an influence of the LHb upon DR neurons may be affected via the D1 receptor.

Schedule control of behavior reinforced by electrical stimulation of the brain.

Electrical stimulation of the brain was used to train rats to respond on random interval schedules. Stimulation was either delayed for 0.5 second and preceded by a brief signal, delayed and unsignaled, or presented contiguously with the response. In every case, responding was maintained on schedules and showed resistance to extinction typical of food-reinforced responding. Priming was never necessary. These data cast doubt on the generality of beliefs about the behavioral effects of brain stimulation reinforcement.