Effects of gonadectomy and androgen supplementation on attention in male rats

Abstract

Androgens are hypothesized to enhance aspects of mnemonic processing. However, it is unclear whether the memory improvement is associated with changes in earlier aspects of information processing, such as attention. The present experiments examined the effects of gonadectomy or supplementation with testosterone or dihydrotestosterone on performance of male rats in a two-lever attention task that required discrimination of visual signals and non-signals. In Experiment 1, Long-Evans rats were trained in the attention task and then underwent gonadectomy or sham-surgery. Postsurgically, animals were tested for 20 sessions in the attention task and then received manipulations designed to increase attentional demands. Gonadectomized and sham-treated animals performed similarly during immediate postsurgical testing and across all manipulations. Finally, the effects of administering the muscarinic receptor antagonist scopolamine (0, 0.1, and 0.2 mg/kg) on attentional performance were assessed for all animals. Scopolamine decreased accuracy of signal detection but did not differentially affect gonadectomized and sham-treated animals. In Experiment 2, a new group of rats (not gonadectomized) was trained to perform the attention task and subsequently administered testosterone (0, 0.1, and 0.5 mg/kg) or dihydrotestosterone (0, 0.1, and 0.5mg/kg) prior to performing the standard version of the attention task and in the presence of a visual distractor. Testosterone (0.5 mg/kg) decreased accuracy on non-signal trials and, at 0.1 mg/kg, decreased latencies to retrieve a reward. Dihydrotestosterone (0.5 mg/kg) decreased accuracy on non-signal trials during visual distractor sessions. The present data do not support the hypothesis that alterations in attention critically mediate androgen-induced changes in mnemonic processing. Supra-physiological androgen levels appear to be capable of impairing attentional processing.

Testosterone impairs the acquisition of an operant delayed alternation task in male rats

“…It is unlikely that the increased latencies in GDX rats were due to an attentional deficit, as this group had longer latencies to respond, yet actually performed better on the DSA task. This conclusion is supported by a previous study in which GDX failed to alter attentional processing in male rats (Johnson and Burk, 2006). Rather, it appears that both the GDX-T and intact-B rats responded more quickly when given the opportunity, a response pattern suggested by other operant studies which found gonadally-intact male rats to respond faster than females when reinforcement is associated with a lever press (Heinsbroek et al, 1987; Van Haaren et al, 1987; Van Hest et al, 1989).…”

Systemic and intrabasalis administration of the orexin-1 receptor antagonist, SB-334867, disrupts attentional performance in rats

“…The decrease in signal detection following systemic SB-334867 could be mediated via the basal forebrain corticopetal cholinergic system, as previous studies have shown that pharmacological blockade of muscarinic receptors (Johnson and Burk 2006;McQuail and Burk 2006) or selective loss of corticopetal cholinergic neurons decrease signal detection in the present task (McGaughy et al 1996). The systemic SB-334867-induced decrease in hits at the 500-ms signal is similar to effects observed in experiments that reported relatively more minor loss of cortical cholinergic inputs (40-70% loss of cortical acetylcholinesterase-positive fibers; McGaughy and Sarter 1998;McGaughy et al 1999).…”

“…In attention-demanding tasks involving pressing one lever following a brief signal and a different lever following no signal, 192 IgG-saporin-induced lesions of basal forebrain corticopetal cholinergic neurons decrease signal detection accuracy (McGaughy et al 1996(McGaughy et al , 2002. In similarly designed tasks, signal detection is also decreased by systemic administration of muscarinic receptor antagonists (McQuail and Burk 2006;Johnson and Burk 2006). Moreover, cortical acetylcholine release is elevated during attentional task performance compared with control tasks (Passetti et al 2000;Dalley et al 2001;Arnold et al 2002).…”

Cognitive effects of hormone therapy in men with prostate cancer

“…Rather, androgen levels in excess of physiologic norms seemed to impair attentional processing. 33 Testosterone actually may decrease activity of the cholinergic system during nonspatial tasks and, thus, work in concert with the antagonism produced by scopolamine. 34 …”