Anterior cerebellar vermal stimulation: effect on behavior and basal forebrain neurochemistry in rat.

Stimulation of the anterior cerebellar vermis (ACV) has been shown to be of therapeutic value in several patients with chronic intractable psychiatric disorders, although the mechanism of action of ACV stimulation remains obscure. The present study sought to clarify how cerebellar stimulation might function by investigating the behavioral and biochemical effects of ACV stimulation in rats. Stimulation was found to increase the amplitude of the acoustic startle response and to produce a borderline enhancement of the potentiated startle effect, results that were interpreted as evidence that ACV stimulation enhances responsiveness to significant environmental cues. A concurrent increase in dopamine turnover and a decrease in serotonin release in the nucleus accumbens suggest possible mechanisms of action of the stimulation. It is proposed that cerebellar stimulation may exert a positive therapeutic effect only in Type II schizophrenia (negative symptomatology), a category of cases possibly associated with an underactive mesolimbic dopamine pathway and, hence, not responsive to neuroleptic treatment.

The effects of radio-frequency lesions of the nucleus accumbens on d-amphetamine-induced locomotor and rearing behavior in rats.

A large body of evidence supports the conclusion that mesolimbic dopaminergic neurons, particularly those that innervate the nucleus accumbens (n. ACC), are important for the expression of amphetamine-stimulated locomotor behavior (ASLB). However, a contradictory report (Wirtshafter et al. 1978), stating that bilateral lesions of the n. ACC fail to block ASLB, was based on a general measure of activity that did not distinguish between locomotion and rearing. In the present study, observer ratings of videotaped responses were used to determine the separate effects of 2.0 mg/kg d-amphetamine (d-AMP) on locomotion and rearing in rats with either sham or radio-frequency lesions of the n. ACC. The n.ACC lesions blocked the locomotor stimulation, but not the increased rearing that follows d-AMP administration. These results support the general conclusion that dopaminergic terminals in the n. ACC are important for the expression of ASLB, and further suggest that d-AMP-stimulated locomotion and rearing are mediated through different neural substrates.

The effect of tail pinch on the acoustic startle response in rats.

A series of 3 experiments was carried out to evaluate the effect of tail pinch (TP) on the amplitude of the acoustic startle response (ASR) in rats. There is a consistent group of pharmacological findings which support the view that the amplitude of the ASR is facilitated by transmission in both dopaminergic and noradrenergic neural systems. It has recently been reported that TP increases cortical norepinephrine release and pars compacta unit activity. It might therefore be expected that TP would facilitate the amplitude of the ASR. This hypothesis was tested in the first experiment. Surprisingly, it was found that TP significantly depressed startle amplitude. In the second experiment if was found that this TP-induced depression in startle amplitude was reduced by damage to the nucleus accumbens and that the amount of reduction correlated with the extent of damage. In the third experiment the generality of the effect of TP on sensorimotor reactivity was evaluated by testing its effect on footshock threshold and airpuff-elicited startle response. TP also depressed responsiveness in these tests. These results are consistent with other observations that the nucleus accumbens plays a role in the modulation of sensorimotor reactivity.

Bilateral lesions of the amygdala attenuate analgesia induced by diverse environmental challenges.

This study was designed to evaluate the role of the amygdala, particularly its central nucleus, in the induction of analgesia elicited by environmental challenges. Rats with large, radiofrequency lesions centered in the central nucleus were found to display significantly attenuated analgesic responses to three different challenges: cat exposure, acute footshock, and re-exposure to an environment associated with footshock. These findings show that the amygdala plays an important role in the elicitation of analgesia by each of the environmental challenges tested. Since the amygdala has been shown to play a critical role in fear, these findings suggest that the analgesia elicited by these challenges involves a substantial fear component. Moreover, the finding that amygdala lesions significantly reduced the analgesia elicited by a non-noxious unconditional stimulus (cat exposure) strongly suggests that these lesions disrupt the expression of analgesia rather than producing a learning impairment. And finally, the findings of this study support the suggestion that fear-elicited analgesia is triggered by activation of a projection from amygdala to periaqueductal gray which forms one component of an integrated 'defensive behavioral system.'

Temporal specificity of fear conditioning: effects of different conditioned stimulus-unconditioned stimulus intervals on the fear-potentiated startle effect.

Separate groups of rats were given 30 pairings of a light (conditioned stimulus, CS) and 500-ms shock (unconditioned stimulus, US) at CS-US intervals of 0, 25, 50, 100, 200, 800, 3,200, 12,800, or 51,200 ms. Other groups had lights and shocks inconsistently paired. The startle reflex was elicited 2-4 days later with a noise burst alone or 25-51,200 ms after light onset. After CS-US pairings over a wide range of intervals (25-51,200 ms), startle was potentiated in testing, sometimes as rapidly as 50 ms after light onset. Magnitude of potentiation and resistance to extinction were generally greater with longer CS-US intervals. In several groups, potentiation was maximal at a test interval that matched the CS-US interval used in training. This temporal specificity sharpened with increasing numbers of training trials but even occurred with a single training trial in which a 51,200-ms CS-US interval was used. The data indicate that even during simple fear conditioning, animals rapidly learn a temporal CS-US relationship. This has important implications for understanding the neural mechanisms of fear conditioning.

Effects of 6-hydroxydopamine and alpha-methyl-para-tyrosine on the acoustic startle response in rats.

The acoustic startle response was measured in rats after depletion of central catecholamines either chronically (through intraventricular injection of 6-hydroxydopamine) or acutely (through intraperitoneal injections of alpha-methyl-para-tyrosine). Chronic depletion resulted in an augmented startle response which could not be attributed to a failure of habituation or enhanced sensitization, while acute depletion depressed startle amplitude. The results were interpreted as evidence that catecholamines normally exert a facilitatory influence on the startle response and that the enhanced response seen in the chronically lesioned animal reflects the potentiation of the role of catecholamine-containing neurons through the development of denervation supersensitivity. This interpretation is consistent with other observations which suggest that catecholamines play a general role in modulating thresholds to aversive events.

Effects of 6-hydroxydopamine on shock-elicited aggression, emotionality and maternal behavior in female rats.

Tests of emotionality and shock-elicited aggression, which have revealed consistent changes in behavior in male rats given 6-hydroxydopamine (6-OHDA), were administered to female rats intraventricularly injected with 250 mug of 6-OHDA to determine whether aspects of the 6-OHDA syndrome are shared by female and male rats. The results confirmed that female rats become hyperemotional as well as hyperaggressive after 6-OHDA, as do males. Using the hypothesis that the behavioral effects of 6-OHDA lesions of catecholamine neurons result from a general reduction in threshold to aversive stimuli, it was predicted that arbitrarily selected stimuli having aversive components should enhance the behavior normally elicited by these stimuli. Stimuli selected for testing were those that normally elicit maternal defensive aggression and maternal retrieval. Both of these behaviors were found to be enhanced in 6-OHDA treated female rats, thus supporting the prediction. These findings were interpreted as inconsistent with the hypothesis that norepinephrine chemically codes specific behaviors, particularly aggressive behavior.

The effects of prenatal nicotine on radial-arm maze performance in rats.

Studies have revealed lasting cognitive impairments, including deficits in attention and learning, in the offspring of women who smoke. Animal models have shown that prenatal nicotine can induce behavioral impairments, including deficits in learning and memory, and one study showed that only females were impaired on a maze task. The purpose of the present experiment was two-fold: 1) to attempt to replicate the reported sex difference in maze learning and 2) to assess the ability of nicotine-treated subjects to learn a maze that placed particularly heavy demands on their attentional capabilities. Pregnant mothers were given 6.0 mg/kg/day of nicotine in their drinking water. Offspring of both sexes were tested following weaning in an 8-arm-radial maze using a confinement procedure. Results showed that prenatal nicotine treatment produced significant impairments in performance in the radial-arm maze. These impairments were seen in animals of both sexes, a finding which challenges the view that only females prenatally treated with nicotine show deficits in maze learning.