Post-session sulpiride infusions within the perifornical region of the lateral hypothalamus enhance consolidation of associative learning

Abstract

Whilst neurons within the lateral hypothalamus are well known to be responsive to the presentation of previously learned associative stimuli, the consolidation of a Pavlovian association is thought to depend in large part upon other brain regions, including the amygdala. The present study addressed this assumption directly, by examining the effect of post-session infusions of sulpiride within the lateral hypothalamus upon the acquisition of a conditioned approach response in an appetitive differential conditioning task. Subjects were exposed to an initially neutral stimulus (CS+), which immediately preceded the availability of a 10% sucrose reward (US). A second, control stimulus (CS ) was also presented. but never in close temporal proximity to the US. The number and duration of alcove approaches were recorded. Immediately following each training session, subjects were infused bilaterally with sulpiride (0, 0.5, 5 microg) in the vicinity of the perifornical region of the lateral hypothalamus. Sulpiride dose-dependently enhanced the rate of acquisition of a conditioned approach response to presentation of the CS+, but was without affect upon approach behaviour during CS(-) or US presentations. Thus, 0.5 microg sulpiride facilitated at an early stage (session 2 onwards) the number of alcove approaches to the CS+, while 5 microg sulpiride enhanced to a greater extent the duration of conditioned approach, particularly during later sessions. A subsequent locomotor test using 0.5 mg/kg d-amphetamine indicated that repeated infusions of the higher dose sulpiride (5 microg), but not the lower dose (0.5 microg), resulted in behavioural sensitisation to administration of the psychomotor stimulant. Acquisition of a novel conditioned instrumental response was not affected by previous exposure to sulpiride. These data suggest that dopamine-sensitive neurons within the lateral hypothalamus may play a significant role in the acquisition of appetitive Pavlovian associations.

Enhanced conditioned inhibition following repeated pretreatment with d -amphetamine

“…However, post-session dopaminergic manipulations of the amygdala have consistently been found to affect selectively the number of conditioned approach responses (Hitchcott et al 1997a, b;Hitchcott and Phillips 1998a). Furthermore, a low dose of post-session sulpiride infused in to the perifornical region of the lateral hypothalamus has been reported to enhance number of CS-associated entries, whereas a dose of sulpiride sufficiently high also to engender behavioural sensitisation was most effective in facilitating the duration of conditioned approach (Phillips and Morutto 1998). As sensitisation would, therefore, seem consistently to produce a different pattern of behavioural improvement to that of direct manipulations of amygdala dopamine, it is possible that an additional neuroanatomical or neurochemical mechanism is in operation.…”

Dissociating the Cognitive Effects of Levodopa versus Dopamine Agonists in a Neurocomputational Model of Learning in Parkinson’s Disease

“…For example, several studies in animals found that D 2 antagonists enhance learning [71,72,73,74]. Similarly, Eyny and Horvitz [74] found that D 2 antagonists enhance learning in rats, whereas D 1 antagonists impair learning.…”

D2 Dopamine Receptor Blockade Immediately Post-training Enhances Retention in Hidden and Visible Platform Versions of the Water Maze

“…Further support for a cholinergic mechanism is provided by evidence that sulpiride's effects on retention of a Y-maze discrimination task in mice depend on muscarinic cholinergic receptors (Gasbarri et al 1997). The presence of at least two potential retention-enhancing mechanisms of action for sulpiride, as well as the different brain regions on which it could be acting (Packard and Teather 1998;Phillips and Morutto 1998;Setlow and McGaugh 1999a), may account for the difference in the most effective dose between the two versions, as well as the appearance of a biphasic doseresponse curve in the hidden platform version. In view of our previous findings that post-training intraaccumbens sulpiride administration impaired retention in the hidden platform version of the water maze (Setlow and McGaugh 1999a), it may seem contradictory that systemic administration enhanced retention in the same version in the present study.…”

“…In one of the few experiments to employ post-training systemic administration of dopamine antagonists in rats, the nonselective antagonist haloperidol impaired later retention of a two-way avoidance task (Gozzani and Izquierdo 1976). In the few studies using post-training intracerebral administration of dopamine antagonists, microinjection of the D2 antagonist sulpiride into either the nucleus accumbens or posteroventral caudate-putamen impaired different measures of retention in the hidden platform version of the Morris water maze (Setlow and McGaugh 1999a,b), whereas the same manipulation of the perifornical region of the lateral hypothalamus enhanced acquisition of a Pavlovian discriminative approach task (Phillips and Morutto 1998).…”