Interaction of nicotinic and histamine H3 systems in the radial-arm maze repeated acquisition task

Abstract

Nicotinic systems have been found in a variety of studies to play important roles in cognitive function. Nicotinic involvement in different aspects of cognitive function such as learning vs. memory may differ. We have found in rats that the spatial repeated acquisition task in the radial-arm maze is significantly improved by low doses of the nicotinic receptor antagonist mecamylamine, the atypical nicotinic receptor ligand lobeline, as well as the α7 nicotinic receptor agonist ARR-17779. Interestingly, nicotine in the same dose range that improves working memory in the win-shift radial maze task was not effective in improving repeated acquisition performance. Nicotinic systems interact with a variety of other neural systems. Differential involvement of these extended effects with learning vs. memory may help explain differential effects of nicotinic drugs with these cognitive functions. Histamine H 3 receptor antagonists have been shown by some studies to improve cognitive function, but others have not found this effect and some have found impairment. Nicotine stimulates the release of histamine. This effect may counter other cascading effects of nicotine in the performance of learning and memory tasks. A specific test of this hypothesis involves our study of nicotine (0.1-0.4 mg/kg) interactions with the histamine H 3 receptor antagonist thioperamide (2.5-10 mg/kg) on learning memory in the repeated acquisition test in the radial-arm maze. The highest dose of thioperamide tested caused a significant choice accuracy impairment, which was most evident during the later portions of the learning curve. The highest dose of nicotine did not change overall errors but did cause a significant impairment in learning over trials. The choice accuracy impairment induced by thioperamide was significantly attenuated by nicotine (0.4 mg/kg). The learning impairment caused by the highest dose of nicotine was significantly attenuated by thioperamide. Thioperamide also caused a slowing of response, an effect, which was attenuated by nicotine coadministration. The repeated acquisition test can help differentiate acute drug effects on learning. Nicotine ant thioperamide effectively reversed each other's choice accuracy impairment even though each by itself impaired accuracy.

The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice

“…In fact, it has been reported that H 3 Rs were involved in the reinforcing properties of certain drugs of abuse, such as, morphine [41], cocaine [10,42], amphetamine [10,43], nicotine [44], and 3,4-methylenedioxymethamphetamine "MDMA" [45]. More particularly, the present findings were in agreement with numerous studies that have demonstrated a relationship between H 3 R and alcohol abuse [2][3][4][5][6]46,47].…”

Modulation of Hippocampus-Dependent Learning and Synaptic Plasticity by Nicotine

“…While a number of studies found that acute nicotine administration (0.07 or 0.14 mg/kg) improved performance in the radial arm maze in rats [123-125], others found either an effect in aged but not young rats [126] or variable effects across experiments [127, 128]. Furthermore, some studies found a lack of an effect at the same doses of nicotine as used in prior studies [129, 130] and one experiment found a trend towards a deficit [131]. …”

Multifunctional Receptor-Directed Drugs for Disorders of the Central Nervous System

“…Levin and colleagues 42 recently studied the effects of nicotine and thioperamide by using the repeated acquisition test in the radial-arm maze. They first determined a dose of nicotine (0.4 mg/kg) that impaired task acquisition, and a dose of thioperamide (10 mg/kg) that increased errors in the task.…”