Repetitive Behaviors in Monkeys Are Linked to Specific Striatal Activation Patterns

Abstract

The spontaneous behavior of humans can be altered dramatically by repeated exposure to psychomotor stimulants. We have developed a primate model for analyzing the neurobiology underlying such drug-induced behavioral changes. We performed ethogram-based behavioral assays on squirrel monkeys given single or multiple cocaine treatments, and in the same monkeys made anatomical plots of striatal neurons that were activated to express early-gene proteins. A final cocaine challenge after chronic intermittent exposure to cocaine induced highly patterned behavioral changes in the monkeys, affecting individual behavioral motifs in distinct ways. In the striatum, the challenge dose induced striosome-predominant expression combined with intense dorsal early-gene expression, especially in the putamen. These patterns of gene expression were highly predictive of the levels of stereotypy exhibited by the monkeys in response to cocaine challenge. The total levels of expression, on the other hand, appeared to reflect increased spontaneous behavioral activation during the drug-free period after the cocaine exposure. We suggest that in the primate, compartmentally and regionally specific striatal activation patterns contribute to the striatal modulation of psychostimulant-induced behaviors. These observations in nonhuman primates raise the possibility that monitoring such basal ganglia activity patterns could help to delineate the neural mechanisms underlying drug-induced repetitive behaviors and related syndromes in which stereotypies are manifest.

Social Modulation of Sequence and Syllable Variability in Adult Birdsong

“…We propose that such changes in catecholamine concentrations in vocal motor circuits, including the AFP, underlie not only the decrease in the variability of syllable structure but also the decrease in the variability of syllable sequencing. Consistent with this perspective are reports that elevated dopamine levels, particularly in nigrostriatal circuits, can increase the stereotypy and repetitiveness of motor expression in rodents and primates (Berridge and Aldridge 2000;Berridge et al 2005;Cromwell et al 1998;reviewed in Ridley 1994;Saka et al 2004).…”

Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia

“…The regulation of movement by the striatum may depend not only on the balance of activity between the matrixbased direct and indirect pathways (23,24), but also on a balance in activity between these pathways and the striosomal pathway (25). For example, an imbalance between compartmentally organized basal ganglia circuits has been suggested to contribute to the generation of repetitive behaviors including motor stereotypies and levodopa induced dyskinesias (14,26). Our findings support the possibility that a differential striosome-matrix pattern of dopaminergic loss could contribute to the genesis of dystonia of the DRD type.…”

Insights into pathophysiology of punding reveal possible treatment strategies

“…66 In the primate model of punding, repetitive behavior induced by repeated exposure to cocaine is associated with patchy striosome-predominant expression of immediate-early genes. 67 Because both the patches and the matrix are regulated by glutamatergic neurons through NMDA receptors, 58 it has been suggested that combined activation of sensitized DA and NMDA receptors may be required to evoke both levodopa-induced dyskinesias and punding in patients with PD. 68 Therefore, there are striking similarities in the neural events that provoke dyskinesias and stereotypies.…”