We have used the interactive two-dimensional model SOCRATES to investigate the thermal and the chemical response of the mesosphere to the changes in greenhouse gas concentrations observed in the past 50 years (CO2, CH4, water vapor, N2O, CFCs), and to specified changes in gravity wave drag and diffusion in the upper mesosphere. When considering the observed increase in the abundances of greenhouse gases for the past 50 years, a cooling of 3--7 K is calculated in the mesopause region together with a cooling of 4--6 K in the middle mesosphere. Changes in the meridional circulation of the mesosphere damp the pure radiative thermal effect of the greenhouse gases. The largest cooling in the winter upper mesosphere-mesopause region occurs when the observed increase in concentrations of greenhouse gases and the strengthening of the gravity wave drag and diffusion are considered simultaneously. Depending on the adopted strengthening of the gravity wave drag and diffusion, a cooling varying from typically 6--10 K to 10--20 K over the past 50 years is predicted in the extratropical upper mesosphere during wintertime. In summer, however, consistently with observations, the thermal response calculated by the model is insignificant in the vicinity of the mesopause. Although the calculated cooling of the winter mesopause is still less than suggested by some observations, these results lead to the conclusion that the increase in the abundances of greenhouse gases alone may not entirely explain the observed temperature trends in the mesosphere. Long-term changes in the dynamics of the middle atmosphere (and the troposphere), including changes in gravity wave activity may have contributed significantly to the observed long-term changes in thermal structure and chemical composition of the mesosphere.