ABSTRACT
Females are significantly more likely to become addicted to nicotine, among other drugs. Intensive research has been conducted on nicotinic acetylcholine receptors as the agents responsible for nicotine addiction. However, the mechanism by which females become more susceptible to addiction and its effects are not known. In an effort to address the sex differences of nicotine addiction, the levels of ovarian hormones, which are significantly more present in females than in males, were monitored as nicotine was administered in rats. Each of the rats’ estrous cycle stages are controlled by differing ovarian hormones. The results showed that a significant number of the rats transitioned into the estrus stage within a significantly short time after nicotine administration. Ovarian hormones are at generally low levels during the estrus stage, so the lack of ovarian hormones as a result of nicotine administration could imply that these hormones are involved in protecting against the effects of addiction.
INTRODUCTION
Pre-pulse Inhibition
Prepulse inhibition (PPI) is a suppression of the startle reflex when a weak stimulus, or a prepulse, precedes the startling stimulus (Kodaira et al, 2013). For example, a rat would receive the prepulse as a kind of preparation for the larger stimulus ahead, and would not be as startled as it would be when responding to a pulse without a prepulse. This inhibitory response is very important for a healthy brain because it prevents sensory overload. A deficiency in PPI means that sensorimotor gating is deficient in the neuronal auditory network, and this results in cognitive dysfunction. Cocaine and schizophreniarelated disorders result in a reduction in PPI, which means that the startle amplitude does not decrease (Martinez, et al., 1999).
The startle reflex operates through the auditory pathway in the brain through a network of sensorimotor gating processes in the auditory cortex, cochlear nuclei, and components of the mesocorticolimbic brain reward circuitry, among others. The brain stem is very important because areas of the brain stem are crucial to the execution of the startle response (Broderick, et al., 2012). The acoustic startle paradigm tests whether PPI has been disrupted or not, and therefore is a model for anxiety and fear-related disorders.
Sex differences have been observed in relation to PPI and startle reflex. In female rats, PPI is reduced more during the proestrus stage than in estrus or diestrus. Males generally have higher PPI than females. Many studies have concluded that ovarian hormones play a significant role in the response to auditory stimuli (Kumari, 2011). In an effort to explain the relationship between ovarian hormones and reduced PPI, one study concluded that either estrogen could reduce PPI because it elevates excitatory neuronal firing at the gate and enhances PPF, or that progesterone protects against PPI reduction, so when progesterone levels are low, PPI can be reduced. PPI was reduced during the luteal phase as compared to the follicular phase. Suppression of PPI was most obvious during mid-luteal elevations of estrogen and progesterone (Becker et al., 2008). From this, it can be concluded that estrogen decreases response in an acoustic startle, with respect to PPI.