Responses of neurons in dorsal striatum during amphetamine-induced focused stereotypy

Abstract

The phase of highly focused, repetitive behavior (stereotypy) induced by amphetamine in rats emerges after an initial period of locomotor activation. To assess the neuronal correlates of this behavioral transition, single-unit activity was recorded from the dorsal striatum of awake, unrestrained rats. Units were first characterized in terms of their responsiveness to spontaneous movement. Various types of motor-related neurons were identified. Some increased activity above resting baseline during specific movements such as forward locomotion or turning of the head, while others were excited during periods of general behavioral activation. Neurons that showed no consistent change in firing rate during overt movement were classified separately. Administration of 5.0 mg/kg d-amphetamine caused a steady increase in the overall neuronal response through both the locomotor and stereotypy phases. An analysis of specific neuronal types, however, revealed distinct, phase-related shifts in firing rate. Locomotor-related neurons discharged rapidly during the early phase of the amphetamine response and then declined toward baseline as focused stereotypy emerged. Cells found to be excited primarily during head movements showed relatively small changes shortly after drug administration but increased markedly in conjunction with intense head-movement activity associated with focused stereotypy. Other neurons, which increased activity nonselectively to a wide range of movements, showed progressive increases in firing rate during both behavioral phases elicited by the drug. Subsequent administration of 1.0 mg/kg haloperidol typically reversed the neuronal changes and blocked amphetamine-induced focused stereotypy. Nonmotor-related cells responded inconsistently to amphetamine, showing an inhibition, excitation, or no change in rate. Previous assessments of neuron-behavior relationships have shown that changes in motor-related neuronal activity are not secondary to amphetamine-induced behavioral changes, though this finding may not apply in all cases. At doses capable of eliciting focused stereotypy, therefore, amphetamine appears to trigger a complex pattern of striatal activity that governs the behavioral response. This conclusion supports steadily increasing evidence that the role of striatal neurons in amphetamine-induced focused stereotypy is shaped by multiple synaptic mechanisms.

An fMRI Study of the Effect of Amphetamine on Brain Activity,

“…The second explanation for the observed effect is that the same neurons that are normally activated by the tasks may have been activated to a greater extent in the presence of amphetamine. This is consistent with the observations in laboratory animals that both amphetamine and cocaine appear to increase the gain, or signal-to-noise ratio, by increasing the electrophysiological activity of individual neurons associated with motor function in rodents (Haracz et al 1993;Rebec et al 1997;White et al 1998). It is not possible to separate these two actions from the present results, and the two actions are not mutually exclusive.…”

Individual Differences in Cocaine- and Amphetamine-Induced Activation of Male Sprague–Dawley Rats: Contribution of the Dopamine Transporter

“…In some cases, stereotyped behavior was manifested as focused head movement and sniffing, whereas in other cases rats circled the chamber in one direction stopping for frequent bouts of rearing behavior. Similar effects induced by this dose of AMPH have been reported previously (eg Rebec et al, 1997) and are mediated by a number of factors including DA receptor sensitivity (Segal and Kuczenski, 1999), non-DA mechanisms (Joyce and Iversen, 1984), and subregions of both the dSTR and NAc (Kelly et al, 1975;Kelley et al, 1988). Owing to our emphasis on 'low-dose' locomotor activating effects of COC and AMPH, we did not analyze the effects of 5 mg/ kg AMPH on DAT function.…”

Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

“…5). In normal rats this pattern of results is often observed after high doses of amphetamine, because: (a) locomotor activity decreases as more intense stereotyped behaviors are preferentially expressed, and (b) locomotor activity frequently re-emerges during a poststereotypy phase (Segal and Kuczenski, 1987;Kuczenski and Segal, 1989;Rebec et al, 1997). Taken together, these unexpected results (we hypothesized that Mn would reduce stereotypy) suggest that early Mn exposure induces long-term neural changes that increase the sensitivity of the nigrostriatal system to amphetamine.…”

“…The integrity of nigrostriatal functioning was also assessed by testing vehicle-and Mn-exposed rats on the accelerating rotorod task and in automated activity chambers. In the latter experiment, rats were pretreated with saline or amphetamine (2 or 4 mg/kg) because psychostimulant-induced motor stereotypies are known to be mediated by the striatum (Jaber et al, 1995;Rebec et al, 1997;Canales and Graybiel, 2000).…”