Circling induced by intra-accumbens amphetamine injections.

Microinjections of d-amphetamine (5.0, 10.0 and 20.0 micrograms/0.5 microliters) into the nucleus accumbens caused reliable dose-dependent circling away from the side of injection. Injections of l-amphetamine were not effective, ruling out non-specific effects of pH, osmolarity and the like and also ruling out noradrenergic actions as explanations of the behavioral effects. Injections of d-amphetamine into the ventral caudate were less potent than those into the nucleus accumbens, suggesting nucleus accumbens rather than more dorsal tissue as the site of this behavioral effect. These data suggest that asymmetrical activation of the nucleus accumbens is a sufficient condition to induce circling behavior and raise questions for the commonly accepted view that asymmetrical activation of the caudate is a necessary condition for dopamine dependent circling behavior.

Facilitation of feeding by nucleus accumbens amphetamine injections: latency and speed measures.

Food-deprived rats were offered food in small meal segments, and latency to initiate feeding and time to complete it were recorded for each segment. Bilateral microinjections of d-amphetamine into nucleus accumbens dramatically increased the mean speed with which meal segments were eaten, but had no reliable effect on mean latency to initiate eating of new segments; l-amphetamine had similar but weaker effects. While mean eating speed was increased, this increase resulted from a decrease in the frequency of slow trials and not from an increase in the absolute speed of the fastest trials. These data suggest that amphetamine facilitates feeding by some other means than simple improvement of the motoric capacity of the animal, and they indicate that nucleus accumbens is an important site for amphetamine's established but not widely appreciated facilitory effects on feeding.

Effects of nucleus accumbens amphetamine on lateral hypothalamic brain stimulation reward.

The effects of amphetamine were examined in a brain stimulation reward paradigm in which response rate was measured across a range of stimulation frequencies. Both low (0.0625 and 0.125 mg/kg) and high (1.0, 2.0 and 4.0 mg/kg) doses of systemic amphetamine decreased the stimulation frequency needed to sustain low rates of responding; high doses decreased the maximal response rates that were sustained by the highest stimulation frequencies. Ipsilateral microinjections (2.5, 5.0 and 10.0 micrograms/0.5 microliter) of D-amphetamine sulfate into the nucleus accumbens also caused shifts to the left of the rate-frequency function; no central dose caused a change in the asymptotic response rate associated with high stimulation frequencies. Contralateral injections of D-amphetamine (10.0 micrograms) also shifted the rate-frequency functions to the left, but were much less potent. Ipsilateral injections of D-amphetamine into the caudate were also less potent, suggesting nucleus accumbens rather than more dorsal tissue as the site of this behavioral action. Also less potent were the effects of L-amphetamine, ruling out non-specific effects of pH, osmolarity and the like and also ruling out noradrenergic actions as explanations of the behavioral effects of the injections. These data suggest that nucleus accumbens is a site of amphetamine's reward-enhancing and threshold-lowering effects on brain stimulation reward.

Opposite effects of unilateral forebrain ablations on ipsilateral and contralateral hypothalamic self-stimulation.

Unilateral ablations of frontal cortex, rostral striatum, nucleus accumbens, septal area and olfactory tubercle decreased ipsilateral hypothalamic self-stimulation; the same ablations had the opposite effect on contralateral self-stimulation. The ablations shifted the function relating response rate to stimulation frequency (rate-frequency function) to the right for ipsilateral self-stimulation and to the left for contralateral self-stimulation, suggesting a reduction and an augmentation, respectively, of the rewarding impact of the stimulation. The inhibition of ipsilateral self-stimulation was neither total nor permanent; 20-30% shifts in threshold were seen at first, but behavior returned to near-normal levels over a period of several weeks. In contrast, the augmentation of contralateral self-stimulation showed no significant change over the same period; in this case the 20-30% shifts in threshold were immediate and permanent. The degree of change in ipsilateral threshold was positively correlated with lesion size; the degree of change in the contralateral threshold was not. Ablations restricted to cortical tissue caused a lesser degree of augmentation of contralateral self-stimulation and had no effect on ipsilateral self-stimulation. The small effects of large ablations on ipsilateral self-stimulation confirm similar observations of Huston and Stellar and their co-workers and raise questions for current theories regarding the role of dopamine in brain stimulation reward. The facilitation of contralateral self-stimulation indicates that brain stimulation reward does not involve a completely lateralized mechanism.

Correlation between behavioral status and cerebral glucose utilization in rats following freezing lesion.

Standard small, superficial freezing lesions placed along the anterior-posterior plane of the left cortex produced behavioral changes in rats. One to 3 days following the lesion, rats showed asymmetries in somatosensory responsiveness, decreases in running wheel activity and difficulty with limb coordination. No changes in spontaneous circling were seen. At the completion of the behavioral testing on day 3 the [14C]2-deoxyglucose method confirmed the presence of widespread depression in local cerebral glucose utilization with cortical areas ipsilateral to the lesion being most affected. At this time the degree of the somatosensory deficit was significantly correlated with the extent of the depression of glucose utilization in the cortical areas of the lesioned hemisphere. At 6 days following the lesion only deficits in limb coordination remained, while local cerebral glucose utilization had returned to within normal limits. It is concluded that the demonstrated behavioral changes were a manifestation of widespread functional depression, as reflected by decreased cortical glucose utilization throughout the lesioned hemisphere.

Pimozide attenuates free feeding: best scores analysis reveals a motivational deficit.

Pimozide treatment (1.0 and 2.0 mg/kg) decreased free feeding in rats. The animals were presented daily with 35 meal segments, each consisting of five 45-mg pellets; pimozide resulted in longer mean latencies to initiate eating, longer mean eating times per segment (duration scores) and more pellets left uneaten. The increase in durations was progressive both within and across test sessions; toward the end of the final session many pellets were left uneaten. Failure to initiate eating of the first pellet of each segment was rare, and was always preceded by failure to eat the fifth pellet of the preceding meal segment. To assess whether either the increase in latencies or the increase in durations reflected an impairment of absolute response capability, 'best scores' in the pimozide and control conditions were compared; the shortest latencies and durations in the pimozide condition were as 'good' as those of the control condition. However, the animals generally produced 'best' scores on fewer trials in the pimozide condition. An exception was on day 1 of testing, when the frequency of 'best' latencies was higher in the pimozide condition. The fact that the 'best' scores under pimozide equalled the 'best' scores under vehicle suggests that the pimozide-treated animals had the motoric capacity to respond normally. The facts that the pimozide-treated animals did not perform to the demonstrated limits of that capacity in a normal percentage of trials and that performance on days 2 and 3 of testing were 'worse' than performance on day 1 of testing suggest that pimozide causes a motivational deficit that has not been widely recognized.