From the Behavioral Pharmacology of Beta-Carbolines to Seizures, Anxiety, and Memory

Abstract

A number of beta-carbolines are inverse agonists of the GABA-A receptor complex, acting on the benzodiazepine site. They show convulsive properties when administered at high doses, anxiogenic properties at moderate doses, and learning-enhancing effects at low doses. These data suggest a possible physiological relationship, through the GABA-A receptor channel, between memory processes, anxiety, and ultimately, in pathological states, epileptic seizures. This relationship seems to be confirmed partially by experiments on mouse strains selected for their resistance (BR) and sensitivity (BS) to a single convulsive dose of a beta-carboline. These two strains also show differences in anxiety and learning abilities. However, some opposite results found while observing the behavior of the two strains suggest that in addition to pharmacologically induced anxiety, there is spontaneous anxiety, no doubt involving other brain mechanisms.

Low and high doses of Norharmane respectively improve and impair learning and memory in streptozotocin-induced rat model of sporadic alzheimer’s disease

“…In conclusion, the effect of NO on learning and memory is dose dependent. Confirming our results, Venaultet al has shown that low doses of β-carboline alkaloids improve learning and memory retention [26].…”

“…The dose of β-carboline required for enhancing memory is usually lower than the dose required for eliciting anxiogenic actions [5,26] and this rule was replicated in our study. Confirming our results, Samardˇzi´c et al have shown that DMCM, a benzodiazepine site inverse agonist, at the dose of 0.1 mg/kg improves active avoidance in the rats [1].…”

“…β-carbolines are assumed to have neuroprotective properties as well as cytotoxic properties [18][19][20], excitation and euphoria [21,22], analgesic effects [23], anticancerous and antibiotic properties [24,25]. It is also suggested that β-carbolines in high doses are epileptogenic, in medium doses anxiogenic, while in low doses, improve learning and memory [26].…”

The effect of CA1 dopaminergic system in harmaline-induced amnesia

“…In the human body, the b-carbolines may be formed from the biogenic amines tryptamine and 5-HT through condensation with aldehydes or a-keto acids (Talhout et al, 2007;Rook et al, 2010). Several investigations indicate a wide spectrum of therapeutic activities for the b-carbolines such as antinociceptive effect (Nenaah, 2010), neuroregulatory effect (Munoz et al, 2000;Splettstoesser et al, 2005;Moura et al, 2006), antibiotic properties (Martin et al, 1997;Hamsa and Kuttan, 2010;Yang et al, 2011), antidepressant-like effect (Herraiz and Chaparro, 2005), learning processes (Venault and Chapouthier, 2007), and excitation (Rommelspacher et al, 1980). The b-carboline alkaloids may act in biological tissues, such as the heart, kidney, liver and brain tissue (Ruiz-Durantez et al, 2001;Splettstoesser et al, 2005;Moura et al, 2006;Rook et al, 2010;Nasehi et al, 2012).…”

Physical versus Social Fear: A Fundamental Dichotomy

“…They can translate into an immobilisation, a "falling back" of the animal on itself ("freezing") or, at the contrary, into an active motor response like flight or fight. In many cases, in the mouse for example, the aggressive tendency is correlated to anxiety (Guillot & Chapouthier, 1996), but there are exceptions (Venault & Chapouthier, 2007). These fear, anxiety, and stress mechanisms can be found in most animals, in all vertebrates in particular.…”